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Interleukin-1 beta Serum Levels is Increased in Antidepressant-Free Elderly Depressed Patients

DINIZ, Breno Satler; TEIXEIRA, Antonio Lucio; TALIB, Leda; GATTAZ, Wagner Farid; FORLENZA, Orestes Vicente
Fonte: LIPPINCOTT WILLIAMS & WILKINS Publicador: LIPPINCOTT WILLIAMS & WILKINS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.83%
Objective: To assess the serum levels of interleukin 1 beta (IL-1 beta) in elderly depressed patients in comparison with nondepressed healthy elderly subjects. Design: Cross-sectional study. Setting: Tertiary memory clinic. Participants: Twenty-three antidepressant-free elderly depressed patients and 44 nondepressed healthy elderly comparison group were enrolled to this study. Measurement: Serum IL-1 beta levels were determined with highly sensitive colorimetric sandwich enzyme-linked immunosorbent assay. Severity of the depressive episode was determined by scores on the Hamilton Depression Scale-21 item and cognitive performance by the scores on the Cambridge Cognition Examination, Mini Mental State Examination clock drawing test, and verbal fluency. Results: IL-1 beta serum levels were increased in elderly patients versus nondepressed elderly (t = 2.21, df = 65, p = 0.04). After categorizing elderly depressed subjects into late onset (LOD) versus early onset (EOD), patients with EOD had the highest IL-1 beta levels, when compared with nondepressed elderly patients and patients with LOD in analysis of variance (F = 4.9, df = 2, 64, p < 0.01). Conclusions: Late-life depression is associated with higher IL-1 beta levels suggesting that increased proinflammatory state may play a role in the physiopathology of depression in the elderly. The authors further show that this might be more prominent in those patients with EOD geriatric depression. (Am J Geriatr Psychiatry 2010; 18: 172-176); Rede Instituto Brasileiro de Neurociencia; FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[02/12633-7]; Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS); CAPES...

Stromal interleukin-1 expression in the cornea after haze-associated injury

BARBOSA, F. L.; CHAURASIA, S. S.; KAUR, H.; MEDEIROS, F. W. de; AGRAWAL, V.; WILSON, S. E.
Fonte: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD Publicador: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.9%
The purpose of this study was to determine whether myofibroblasts or other cells in the stroma in the cornea produce interleukin (IL)-1 alpha or IL-1 beta that could modulate myofibroblast viability in corneas with haze after photorefractive keratectomy (PRK). Twenty-four female rabbits had haze-generating PRK for 9 diopters of myopia and were sacrificed at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims were removed, frozen in OCT at -80 degrees C, and analyzed by immunocytochemistry using primary antibodies to IL-1 alpha, IL-1 beta and alpha smooth muscle actin (SMA). Double immunostaining was performed for the co-localization of SMA with IL-1 alpha or IL-1 beta. Central dense haze and peripheral slight haze regions of each cornea were analyzed. SMA+ cells that expressed IL-1 alpha protein were detected in both regions of the corneas at most time points following PRK. However, in the haze region at the 1,3 and 4 week time points, significantly more (p < 0.01) SMA cells did not express IL-1 alpha. Also, in the haze region at all three time points, significantly more (p < 0.01) SMA- cells than SMA+ cells expressed interleukin-1 alpha protein. IL-1 beta expression patterns in SMA+ and SMA- stromal cells was similar to that of IL-1 alpha after PRK. Previous studies have demonstrated that IL-1 alpha or IL-1 beta triggers myofibroblast apoptosis in vitro...

Association between mannose-binding lectin and interleukin-1 receptor antagonist gene polymorphisms and recurrent vulvovaginal candidiasis

Kaoro Horie Wojitani, Maria Dulce; de Aguiar, Lana Maria; Baracat, Edmond Chada; Linhares, Iara Moreno
Fonte: SPRINGER HEIDELBERG; HEIDELBERG Publicador: SPRINGER HEIDELBERG; HEIDELBERG
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.81%
Objective The influence of functional polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL-1ra) on recurrent vulvovaginal candidiasis (RVVC) were examined in an urban Brazilian population. Methods DNA was isolated from buccal swabs of 100 women with RVVC and 100 control women and tested by gene amplification for a single nucleotide polymorphism in codon 54 of the MBL2 gene and for a length polymorphism in intron 2 of the IL1RN gene. Genotype and allele frequencies were compared between groups. Results The frequency of the variant MBL2 B allele, associated with reduced circulating and vaginal MBL concentrations, was 27.0% in RVVC and 8.5% in control women (p < .0001). The MBL2 B, B genotype was present in 12% of RVVC patients and 1% of controls (p = .0025). The IL1RN 2 allele frequency, associated with the highest level of unopposed IL-1 beta activity, was 24.0% in RVVC and 23.4% in controls. The IL1RN genotype distribution was also similar in both groups. Conclusion Carriage of the MBL2 codon 54 polymorphism, but not the IL1RN length polymorphism, predisposes to RVVC in Brazilian women.

Impairment of the hematological response and interleukin-1β production in protein-energy malnourished mice after endotoxemia with lipopolysaccharide

Fock, Ricardo Ambrosio; Vinolo, M.A.R.; Blatt, S.L.; Garcia, Primavera Borelli
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.84%
The objectives of this study were to determine if protein-energy malnutrition (PEM) could affect the hematologic response to lipopolysaccharide (LPS), the interleukin-1β (IL-1β) production, leukocyte migration, and blood leukocyte expression of CD11a/CD18. Two-month-old male Swiss mice were submitted to PEM (N = 30) with a low-protein diet (14 days) containing 4% protein, compared to 20% protein in the control group (N = 30). The total cellularity of blood, bone marrow, spleen, and bronchoalveolar lavage evaluated after the LPS stimulus indicated reduced number of total cells in all compartments studied and different kinetics of migration in malnourished animals. The in vitro migration assay showed reduced capacity of migration after the LPS stimulus in malnourished animals (45.7 ± 17.2 x 10(4) cells/mL) compared to control (69.6 ± 7.1 x 10(4) cells/mL, P ≤ 0.05), but there was no difference in CD11a/CD18 expression on the surface of blood leukocytes. In addition, the production of IL-1β in vivo after the LPS stimulus (180.7 pg·h-1·mL-1), and in vitro by bone marrow and spleen cells (41.6 ± 15.0 and 8.3 ± 4.0 pg/mL) was significantly lower in malnourished animals compared to control (591.1 pg·h-1·mL-1, 67.0 ± 23.0 and 17.5 ± 8.0 pg/mL...

Avaliação da frequência do polimorfismo nos genes que codificam a lecitina ligadora da manose (MBL) e o antagonista do receptor da interleucina-1 (IL1-Ra) em mulheres portadoras de candidíase vulvovaginal recorrente; Frequency of polymorphisms in the genes coding for mannose binding ligation (MBL) and Interleukin-1 receptor antagonist (IL1- Ra) in women with recurrent vulvovaginal candidiasis

Wojitani, Maria Dulce Caoro Horie
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 31/05/2011 Português
Relevância na Pesquisa
65.82%
A candidíase vulvovaginal corresponde a uma das mais frequentes infecções do trato reprodutivo. Estima-se que 75% das mulheres na idade reprodutiva experimentarão pelo menos um episódio de candidíase vulvovaginal durante suas vidas, a maioria evoluirá com episódios infrequentes, entretanto, 5% sofrerão recorrência, ou seja, quatro ou mais episódios de candidíase vulvovaginal comprovadas clínica e laboratorialmente no período de 1ano. Os mecanismos pelos quais as recorrências ocorrem ainda são pouco conhecidos, estando provavelmente relacionados à alterações na imunidade local. O presente estudo teve como objetivo avaliar as associações entre os polimorfismos nos genes que codificam a lecitina ligadora de manose (MBL) e do antagonista do receptor da interleucina 1 (IL1-Ra) com a candidíase vulvovaginal recorrente (CVVR) em mulheres brasileiras. Foram estudadas 100 mulheres portadoras de CVVR atendidas no Serviço de Imunologia Genética e Infecções do Trato Reprodutivo da Disciplina de Ginecologia da Faculdade de Medicina da Universidade de São Paulo. Para a análise dos polimorfismos nos genes que codificam para a MBL e o IL1-Ra realizou-se coleta de células bucais que foram enviadas para Division of Immunology and Infectious Diseases of Weill Medical College of Cornell University Resultados: Mulheres com candidíase vulvovaginal recorrente apresentaram maior frequência de polimorfismo no códon 54 do gene que codifica a MBL quando comparadas a mulheres saudáveis. Não foram observadas diferenças estatisticamente significativas na frequência do polimorfismo do gene que codifica o IL1-Ra entre os grupos estudados; Vulvovaginal candidiasis is the most common genital infection in women during their childbearing years. About 75% of women suffer at least one syntomatic episode during their lives. Most of them will have infrequent episodes...

Evidence of a relationship between aversive learning and hippocampal interleukin 1 beta levels in neonatal handled rats

Nunes, Wagner de Paula
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Trabalho de Conclusão de Curso Formato: application/pdf
Português
Relevância na Pesquisa
65.92%
The Neonatal Handling (NH) model presents a “blunted” corticosterone response to stress as well as an enhancement in contextual fear tasks. So the aim of this work was to examine a possible relationship between diminished imunosuppression over Interleukin 1 beta (IL-1) hippocampal levels and enhancement in aversive learning. To achieve that, we subjected male handled Wistar rats 30-35 and 90 days old to an inhibitory avoidance task, comparing the avoidance scores with respective hippocampal IL-1 levels at different time points. We found that handled adult animals learned the aversive task concomitantly with higher levels of hippocampal interleukin 1 beta 2h after footshock, while control animals showed diminished aversive learning and lower IL-1 beta levels at the same time. In the other hand, both handled and non-handled juvenile rats learned the aversive task, with no signal of immunosuppressant efect over interleukin 1 beta. However, basal levels of IL-1 beta were different between handled and non-handled animals in both ages, pointing a novel neuroimmunomodulation involvement to the NH model.

Impairment of the hematological response and interleukin-1β production in protein-energy malnourished mice after endotoxemia with lipopolysaccharide

Fock,R.A.; Vinolo,M.A.R.; Blatt,S.L.; Borelli,P.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2012 Português
Relevância na Pesquisa
65.84%
The objectives of this study were to determine if protein-energy malnutrition (PEM) could affect the hematologic response to lipopolysaccharide (LPS), the interleukin-1β (IL-1β) production, leukocyte migration, and blood leukocyte expression of CD11a/CD18. Two-month-old male Swiss mice were submitted to PEM (N = 30) with a low-protein diet (14 days) containing 4% protein, compared to 20% protein in the control group (N = 30). The total cellularity of blood, bone marrow, spleen, and bronchoalveolar lavage evaluated after the LPS stimulus indicated reduced number of total cells in all compartments studied and different kinetics of migration in malnourished animals. The in vitro migration assay showed reduced capacity of migration after the LPS stimulus in malnourished animals (45.7 ± 17.2 x 10(4) cells/mL) compared to control (69.6 ± 7.1 x 10(4) cells/mL, P ≤ 0.05), but there was no difference in CD11a/CD18 expression on the surface of blood leukocytes. In addition, the production of IL-1β in vivo after the LPS stimulus (180.7 pg·h-1·mL-1), and in vitro by bone marrow and spleen cells (41.6 ± 15.0 and 8.3 ± 4.0 pg/mL) was significantly lower in malnourished animals compared to control (591.1 pg·h-1·mL-1, 67.0 ± 23.0 and 17.5 ± 8.0 pg/mL...

Bidirectional signaling between stromal and hemopoietic cells regulates interleukin-1 expression during human osteoclast formation

Haynes, D.; Atkins, G.; Loric, M.; Crotti, T.; Geary, S.; Findlay, D.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Artigo de Revista Científica
Publicado em //1999 Português
Relevância na Pesquisa
65.85%
Interleukin-1 (IL-1) has been shown to promote osteoclast (OC) differentiation, in addition to acting as a survival factor for mature osteoclasts. In this study, we investigate the expression of IL-1 during human osteoclast formation, taking advantage of a recently reported in vitro culture system that generates human OC from precursors in the peripheral blood mononuclear cell (PBMC) fraction, in the presence of murine stromal cells. This system enabled us to use species-specific probes and immunoassays to determine the respective cytokine contributions of the stromal cell and hemopoietic cell populations. Formation of functional osteoclasts occurred in cocultures of human PBMC and ST-2 cells for up to 21 days in the presence of 1α,25(OH)2-vitamin D3, dexamethasone, and recombinant human macrophage colony-stimulating factor (rhM-CSF). Total RNA was prepared at intervals during the cocultures and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using primers designed to amplify specifically the mRNA species corresponding to the respective murine or human IL-1α and IL-1β isoforms. Using human-specific primers, it was found that the hemopoietic cell component expressed both IL-1α and IL-1β mRNA. Specific measurement of secreted human IL-1β protein showed greatly augmented levels in coculture compared with hemopoietic cells grown in the absence of ST-2 cells...

Early expression and cellular localization of proinflammatory cytokines interleukin-1[beta], interleukin-6, and tumor necrosis factor-[alpha] in human traumatic spinal cord injury

Yang, L.; Blumbergs, P.; Jones, N.; Manavis, J.; Sarvestani, G.; Ghabriel, M.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2004 Português
Relevância na Pesquisa
65.99%
Study Design. Post-traumatic inflammatory response was studied in 11 human cases of acute spinal cord contusion injury. Objectives. To examine the inflammatory cellular response and the immunocytochemical expression and localization of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha]in human spinal cord after contusion injury. Summary of Background Data. The post-traumatic inflammatory response plays an important role in secondary injury mechanisms after spinal cord injury, and inter-leukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] are key inflammatory mediators. Methods. The study group comprised 11 patients with spinal cord contusion injury and 2 normal individuals. Histologic and immunocytochemical assessments were undertaken to evaluate the inflammatory cellular response and the immunoexpression of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] in the injured human spinal cord. The cellular sources of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] were elucidated by immunofluorescence double-labeled confocal imaging. Results. Increased immunoreactivity of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha]was detected in neurons 0.5 hour after injury...

Localisation of mRNA for interleukin-1 receptor and interleukin-1 receptor antagonist in the rat ovary

Wang, L.; Brannstrom, M.; Cui, K.H.; Simula, A.; Hart, R.; Maddocks, S.; Norman, R.
Fonte: Society for Endocrinology Publicador: Society for Endocrinology
Tipo: Artigo de Revista Científica
Publicado em //1997 Português
Relevância na Pesquisa
65.89%
Interleukin-1 (IL-1) is a multifunctional cytokine with profound effects on ovarian function. The effects of IL-1 on ovarian steroidogenesis have been demonstrated in several species. IL-1 mRNA levels are increased in the thecal layer of the ovulating follicle and IL-1β has been shown to induce ovulations in vitro. In this study we have investigated the presence and distribution of the mRNAs for type I IL-1 receptor (IL-1RtI) and for the naturally occurring IL-1 receptor antagonist (IL-1ra) in ovaries of adult cycling rats, to elucidate the target cells for IL-1 action. We have demonstrated the presence of mRNA for both substances by in situ hybridisation and reverse transcription PCR. mRNA for IL-1RtI was not found in primordial follicles but was abundant in the granulosa and thecal layer in developing follicles with stronger signals in the granulosa layer. In the preovulatory and ovulatory follicles, there was a further increase in the signal for IL-1RtI mRNA in the thecal layer compared with the granulosa layer. Corpora lutea were weakly positive at all stages and atretic follicles were largely negative. No mRNA was detected in oocytes of any stage. mRNA for IL-1ra showed a similar distribution to that of IL-1RtI. The changes in distribution suggest an action of IL-1 on rat granulosa cells during follicular development and on thecal cells during ovulation.; L-J Wang...

The Interleukin 1 Beta (IL1B) Gene Is Associated with Failure to Achieve Remission and Impaired Emotion Processing in Major Depression

Baune, B.; Dannlowski, U.; Domschke, K.; Janssen, D.; Jordan, M.; Ohrmann, P.; Bauer, J.; Biros, E.; Arolt, V.; Kugel, H.; Baxter, A.; Suslow, T.
Fonte: Elsevier Science Inc Publicador: Elsevier Science Inc
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
Relevância na Pesquisa
65.83%
Background: Accumulating evidence suggests the involvement of inflammatory processes and cytokines in particular in the pathophysiology of major depression (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been suggested as a predictor of treatment response. This study investigated the association between genetic variants of the interleukin 1 beta (IL1B) gene and amygdala and ACC responsiveness to emotional stimuli and response to antidepressant treatment. Methods: In this analysis, 256 Caucasian patients with MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6 weeks was defined as remission (≤ 7 on the Hamilton Rating Scale for Depression–21-question) and response (>50% decrease on Hamilton Rating Scale for Depression–21-question). Brain activity under visual presentation of emotional faces was assessed in a subsample of 32 depressed patients by means of functional magnetic resonance imaging at 3 T. Results: Pharmacogenetic analyses show significant associations of the GG genotypes of single nucleotide polymorphisms (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2–4.3) and rs1143643 (odds ratio = 3.1; 95% confidence interval 1.3–7.8) (compared with the AA genotype) with nonremission after 6 weeks. The imaging analyses show that the number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with reduced responsiveness of the amygdala and ACC to emotional stimulation. Conclusions: The present study suggests a negative effect of the IL1B gene on pharmacological response and amygdala and ACC function involving the same genotypes of two SNPs (rs16944...

Association of Interleukin-1 gene polymorphisms with central obesity and metabolic syndrome in a coronary heart disease population

Carter, K.; Hung, J.; Powell, B.; Wiltshire, S.; Foo, B.; Leow, Y.; McQuillan, B.; Jennens, M.; McCaskie, P.; Thompson, P.; Beilby, J.; Palmer, L.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
Relevância na Pesquisa
65.85%
The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in the Interleukin-1 (IL-1) gene family are associated with central obesity and metabolic syndrome in a coronary heart disease population. The IL-1α C-889T (rs1800587) and IL-1β +3954 (rs1143634) SNPs were studied in a Western Australian coronary heart disease (CHD) population (N = 556). Subjects who were TT homozygous at either SNP had larger waist circumference (IL-1α: 1.8 cm greater, P = 0.04; IL-1β: 4 cm greater, P = 0.0004) compared with major allele homozygotes. Individuals with two copies of the IL-1α:IL-1β T:T haplotype had greater waist circumference (4.7 cm greater, P = 0.0001) compared to other haplotypes. There was a significant interaction between the IL-1β SNP and BMI level on waist circumference (P = 0.01). When the cohort was stratified by median BMI, TT carriers for IL-1β with above median BMI had greater waist circumference (6.1 cm greater, P = 0.007) compared to baseline carriers, whilst no significant association was seen in the below median group. Similarly, when the cohort was stratified by median fibrinogen level (IL-1α interaction P = 0.01; IL-1β interaction P = 0.04), TT carriers for both SNPs in the above median fibrinogen group had greater waist circumference (IL-1α 2.7 cm greater...

CNS immune signalling and drug addiction: the role of interleukin-1 beta.

Liu, Liang
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2011 Português
Relevância na Pesquisa
65.85%
Opioid and alcohol dependencies are significant public health problems worldwide. The causes of drug dependence are complex, comprising both genetic and environmental factors. Recent evidence from animal models has shown that opioid-/alcohol-induced proinflammation within the central nervous system (CNS) plays a contributing role in the development of dependence. Proinflammatory cytokines, such as interleukin-1 beta (IL-1β), may be involved in the development of opioid/alcohol dependence. Thus, genetic polymorphisms in the proinflammatory cytokine genes that alter their expression and/or function may alter the risk of dependence in humans. Previously, genetic polymorphisms in two genes, IL-1B and IL-1RN, which encode for IL-1β and IL-1 receptor antagonist (IL-1Ra), respectively, were shown to be associated with altered risk of alcohol dependence. However, this has yet to be examined in an opioid dependent population. Therefore, the first major aim of this thesis was to examine the possible association between genetic variability of IL-1B and IL-1RN in opioid dependent and healthy control populations. In order to confirm the previous study within the Australian context, this thesis also examined the variability of the IL-1B and IL-1RN genetic polymorphisms in an Australian alcohol dependent population. Genomic DNA from opioid dependent subjects (n = 60)...

Variant interleukin 1 receptor antagonist gene alleles in sudden infant death syndrome

Highet, A.; Gibson, C.; Goldwater, P.
Fonte: British Med Journal Publ Group Publicador: British Med Journal Publ Group
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
Relevância na Pesquisa
65.81%
Objective: To investigate if carriage of interleukin 1 (IL-1) receptor antagonist gene variants are associated with sudden infant death syndrome (SIDS) in a large cohort of case–control demographically matched infants. Design: 118 SIDS and 233 control infants, who were matched to each SIDS infant by date of birth, sex, birth weight (±500 g), gestational age and ethnicity, were genotyped for an IL-1RN 89 bp tandem repeat polymorphism and analysed for significant associations. Results: No significant difference in genotype frequencies was observed between low and normal birthweight infants and year of birth (1987–1994, when the SIDS incidence was higher). In infants born between 1987 and 1994, an association was observed with SIDS and allele 2 where 18% of SIDS infants carried the 2/2 genotype compared with 9% of controls (χ2 p=0.026, OR 2.46). Allele 3 was found at a low frequency, but was significantly more common in SIDS infants (3.1%) compared with controls (0.9%, Fisher's exact p=0.04, OR 3.76). Conclusion: The higher prevalence of IL-1RN allele 2, which predisposes to poor outcomes from infection, in SIDS infants born between 1987 and 1994 (ie, prior to the dramatic decrease in SIDS incidence) suggests that the high incidence during this period could point to infection playing a role in aetiology. An association of IL-1RN allele 3 with SIDS was also found...

HIV-1 induces NALP3-inflammasome expression and interleukin-1 beta secretion in dendritic cells from healthy individuals but not from HIV-positive patients

Pontillo, Alessandra; Silva, Lais T.; Sumida, Telma Miyuki Oshiro; Finazzo, Claudia; Crovella, Sergio; Duarte, Alberto Jose da Silva
Fonte: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA Publicador: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.84%
Objective: NALP3-inflammasome is an innate mechanism, alternative to type-1 interferon, which is able to recognize nucleic acids and viruses in the cytoplasm and to induce pro-inflammatory response. Here, we hypothesized the involvement of inflammasome in the early defense against HIV-1 and in the full maturation of dendritic cells: for this, we evaluated the response of dendritic cells pulsed with HIV-1 in terms of inflammasome activation in healthy donors. Moreover, inflammasome response to HIV was evaluated in HIV-infected individuals. Design and methods: Monocyte-derived dendritic cells isolated from 20 healthy individuals (HC-DC) and 20 HIV-1-infected patients (HIV-DC) were pulsed with alditrithiol-2-inactivated HIV-1. We then analyzed inflammasome genes expression and interleukin-1 beta (IL-1 beta) secretion. Results: In HC-DC, HIV-1 induced higher NLRP3/NALP3 mRNA expression compared with other inflammasome genes such as NALP1/NLRP1 or IPAF/NLRC4 (P < 0.001). This augmented expression was accompanied by CASP1-increased and IL1B-increased mRNA levels and by a significant increment of IL-1b secretion (P < 0.05). Otherwise, HIV-1 failed to activate inflammasome and cytokine production in HIV-DC. HIV-DC showed an increased NLRP3/NALP3 basal expression...

Targeting Interleukin-1β Reduces Leukocyte Production After Acute Myocardial Infarction

Sager, Hendrik B.; Heidt, Timo; Hulsmans, Maarten; Dutta, Partha; Courties, Gabriel P; Sebas, Matthew; Wojtkiewicz, Gregory R.; Tricot, Benoit; Iwamoto, Yoshiko; Sun, Yuan; Weissleder, Ralph; Libby, Peter; Swirski, Filip K.; Nahrendorf, Matthias
Fonte: Ovid Technologies (Wolters Kluwer Health) Publicador: Ovid Technologies (Wolters Kluwer Health)
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.92%
Background—Myocardial infarction (MI) is an ischemic wound that recruits millions of leukocytes. MI-associated blood leukocytosis correlates inversely with patient survival, yet the signals driving heightened leukocyte production after MI remain incompletely understood. Methods and Results—With the use of parabiosis surgery, this study shows that soluble danger signals, among them interleukin-1β, increase bone marrow hematopoietic stem cell proliferation after MI. Data obtained in bone marrow reconstitution experiments reveal that interleukin-1β enhances hematopoietic stem cell proliferation by both direct actions on hematopoietic cells and through modulation of the bone marrow’s hematopoietic microenvironment. An antibody that neutralizes interleukin-1β suppresses these effects. Anti-interleukin-1β treatment dampens the post-MI increase in hematopoietic stem cell proliferation. Consequently, decreased leukocyte numbers in the blood and infarct reduce inflammation and diminish post-MI heart failure in ApoE–/– mice with atherosclerosis. Conclusions—The presented insight into post-MI bone marrow activation identifies a mechanistic target for muting inflammation in the ischemically damaged heart.

Novel epicatechin derivatives with antioxidant activity modulate interleukin-1β release in lipopolysaccharide-stimulated human blood

Mitjans, Montserrat; Martínez, Verónica; Campo, Jaime del; Abajo, Celia; Lozano, Carles; Torres, Josep Lluís; Vinardell, M. Pilar
Fonte: Elsevier Publicador: Elsevier
Tipo: Artículo Formato: 22195 bytes; application/pdf
Português
Relevância na Pesquisa
65.81%
4 pages, 3 figures.-- PMID: 15380193 [PubMed].-- Printed version published Oct 18, 2004; We examine the potential antioxidant activity and the immune function of new epicatechin conjugates obtained by depolymerization of grape polymeric flavanols in the presence of cysteamine or cysteine. When incubated with an erythrocyte suspension, flavanols protected the erythrocyte membrane from hemolysis induced by 2,2′-azo-bis(2-amidinopropane)dihydrochloride (AAPH), an azo free radical initiator. The inhibitory effect was concentration-dependent and the IC50 was 119.8 μM for epicatechin, and 74.9 and 89.4 μM for the cysteine and cysteamine derivatives, respectively. These compounds were tested for their antioxidant activity and their capacity to modulate interleukin-1β (IL-1β), which is currently considered to be the major cytokine factor influencing the acute phase of the inflammatory response. At concentrations up to 20 μM, epicatechin and its derivatives inhibited the production of IL-1β in whole blood incubated in the presence of E. coli lipopolysaccharide (LPS), in a concentration-dependent manner. The most active compound was the cysteamine derivative.; This work was supported by grant PPQ2003-06602-C04-01 from ‘Ministerio de Ciencia y Tecnología’...

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

Interleukin 1 Genetics Consortium; Freitag, Daniel F.; Butterworth, Adam S.; Willeit, Peter; Howson, Joanna M. M.; Burgess, Stephen; Kaptoge, Stephen; Young, Robin; Ho, Weang Kee; Wood, Angela M.; Sweeting, Michael; Spackman, Sarah; Staley, James R.; Ramo
Fonte: Elsevier Publicador: Elsevier
Tipo: Article; published version
Português
Relevância na Pesquisa
65.9%
This is the final version. It was first published by Elsevier at http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2815%2900034-0/fulltext.; Background:To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods: We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1? and IL-1?); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453?411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746?171 total participants). Findings: For each IL1RN minor allele inherited...

Senescent Vascular Smooth Muscle Cells Drive Inflammation Through an Interleukin-1??Dependent Senescence- Associated Secretory Phenotype

Gardner, Sarah E.; Humphry, Melanie; Bennett, Martin R.; Clarke, Murray C. H.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Article; published version
Português
Relevância na Pesquisa
65.92%
This is the final version of the article. It first appeared from Lippincott Williams & Wilkins via http://dx.doi.org/10.1161/ATVBAHA.115.305896; OBJECTIVE: Vascular smooth muscle cells (VSMCs) that become senescent are both present within atherosclerotic plaques and thought to be important to the disease process. However, senescent VSMCs are generally considered to only contribute through inaction, with failure to proliferate resulting in VSMC- and collagen-poor unstable fibrous caps. Whether senescent VSMCs can actively contribute to atherogenic processes, such as inflammation, is unknown. APPROACH AND RESULTS: We find that senescent human VSMCs develop a proinflammatory state known as a senescence-associated secretory phenotype. Senescent human VSMCs release high levels of multiple cytokines and chemokines driven by secreted interleukin-1? acting in an autocrine manner. Consequently, the VSMC senescence-associated secretory phenotype promotes chemotaxis of mononuclear cells in vitro and in vivo. In addition, senescent VSMCs release active matrix metalloproteinase-9, secrete less collagen, upregulate multiple inflammasome components, and prime adjacent endothelial cells and VSMCs to a proadhesive and proinflammatory state. Importantly...

Interleukin-1? Activity in Necrotic Endothelial Cells is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2; Implications for Allograft Rejection

Gardner, Sarah E.; Humphry, Melanie; Bennett, Martin R.; Clarke, Murray C. H.
Fonte: ASBMB Publicador: ASBMB
Tipo: Article; published version
Português
Relevância na Pesquisa
65.93%
This is the final version of the article. It first appeared from ASBMB via http://dx.doi.org/10.1074/jbc.M115.667915; Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1?, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (3 VSMCs). Similarly, IL-1? released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1? requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1? activity upon necrosis. However, TNF? or IL-1 induce significant levels of active IL-1? in EC necrotic lysates without alteration in protein level. Increased activity requires cleavage of IL-1? by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1? associates with interleukin-1 receptor-2 (IL-1R2), and this association is decreased by TNF? or IL-1 and requires caspase activity. Thus, TNF? or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves IL-1R2, allowing IL-1? dissociation and subsequent processing by calpain. Importantly...