TNF-Α, IL-1β and IL-6 Cytokine Gene Expression in Synovial Fluid of Rheumatoid Arthritis and Osteoarthritis Patients and Their Relationship with Gene Polymorphisms

2016 ◽  
Vol 06 (01) ◽  
Author(s):  
Syed Shafiaa ◽  
Zafar Amin Shaha
2010 ◽  
Vol 298 (1) ◽  
pp. C171-C181 ◽  
Author(s):  
Zachary A. Cooper ◽  
Arundhati Ghosh ◽  
Aditi Gupta ◽  
Tapan Maity ◽  
Ivor J. Benjamin ◽  
...  

We previously showed that exposure to febrile-range temperatures (FRT, 39.5–40°C) reduces LPS-induced TNF-α expression, in part through the direct interaction of heat shock factor-1 (HSF1) with the TNF-α gene promoter. However, it is not known whether exposure to FRT also modifies more proximal LPS-induced signaling events. Using HSF1-null mice, we confirmed that HSF1 is required for FRT-induced repression of TNF-α in vitro by LPS-stimulated bone marrow-derived macrophages and in vivo in mice challenged intratracheally with LPS. Exposing LPS-stimulated RAW 264.7 mouse macrophages to FRT reduced TNF-α expression while increasing IL-1β expression despite the two genes sharing a common myeloid differentiation protein-88 (MyD88)-dependent pathway. Global activation of the three LPS-induced signaling intermediates that lead to cytokine gene expression, ERK and p38 MAPKs and NF-κB, was not affected by exposing RAW 264.7 cells to FRT as assessed by ERK and p38 phosphorylation and NF-κB in vitro DNA-binding activity and activation of a NF-κB-dependent synthetic promoter. However, chromatin immunoprecipitation (ChIP) analysis demonstrated that exposure to FRT reduced LPS-induced recruitment of NF-κB p65 to the TNF-α promoter while simultaneously increasing its recruitment to the IL-1β promoter. These data suggest that FRT exerts its effects on cytokine gene expression in a gene-specific manner through distal effects on promoter activation rather than proximal receptor activation and signal transduction.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 360-361
Author(s):  
Sharon A Norton ◽  
Amanda A Adams

Abstract Senior horses often exhibit chronic inflammation and decreased immune responses. Dietary Saccharomyces cerevisiae fermentation product (SCFP; Diamond V, Cedar Rapids, IA) has been shown to affect immune responses in several species. This study aimed to evaluate SCFP-mediated immune function in senior horses. Sixteen horses (24.8 ± 3.0 y; BW = 545.8 ± 61.9 kg) were allotted to two treatments: CON (n = 8; no SCFP supplementation) and SCFP top dressed onto a common concentrate for 56 d (21 g/d; n = 8). Body condition score (BCS), BW, whole blood cytokine (INF-ɣ, TNF-α, IL-1β, IL-6, IL-10, IL-4, IL-8, IL-13, IL-17) and COX-1 and COX-2 gene expression were measured at d 0, 42, 49 and 56. Horses were challenged with a monovalent influenza vaccine at d 42 (MIV; Fluvacc Innovator; Zoetis Animal Health, Parsippany, NJ). Pre-MIV (d 0–42) and post-MIV (d 42–56) responses were analyzed using general mixed model procedures. Pre-MIV, BW tended to increase (P = 0.09) over time. Expression of IL-10 tended to be lower for SCFP than CON (P = 0.09) and IL-13 expression decreased over time (P < 0.05). Post-MIV, BCS linearly increased over time (P = 0.006) while TNF-α tended to increase at d 49 and return to d 42 levels by d 56 (P = 0.06). Both INF-ɣ and IL-10 expression were lower for SCFP vs CON (P < 0.05). Gene expression of COX-2 tended to decrease (P = 0.06) at d 49 and return to the d 42 baseline by d 56. Gene expression of IL-13 tended to decrease with SCFP but increased with CON at d 49 with both returning to d 42 levels by d 56 (P = 0.08). Influenza H1 titers increased over time post-vaccination (P < 0.001) with no difference between treatments. Dietary SCFP may modulate pro-inflammatory and anti-inflammatory cytokine gene expression in senior horses.


2005 ◽  
Vol 288 (4) ◽  
pp. E741-E747 ◽  
Author(s):  
Tongjian You ◽  
Rongze Yang ◽  
Mary F. Lyles ◽  
Dawei Gong ◽  
Barbara J. Nicklas

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-α, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 ± 0.8 kg/m2; age, 57 ± 1 yr). A subset of these women without diabetes ( n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin ( r = −0.46, P < 0.05) and tended to be negatively related to adiponectin ( r = −0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin ( r = 0.69, P < 0.01), 2-h insulin ( r = 0.56, P < 0.05), and HOMA index ( r = 0.59, P < 0.05) correlated positively with TNF-α gene expression; fasting insulin ( r = 0.54, P < 0.05) was positively related to, and 2-h insulin ( r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area ( r = −0.56, P < 0.05) was negatively related to, and insulin area ( r = −0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-β-actin ratio, 2.26 ± 0.46 vs. 3.31 ± 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.


2000 ◽  
Vol 7 (5) ◽  
pp. 769-773 ◽  
Author(s):  
Elizabeth Crabb Breen ◽  
Matthew McDonald ◽  
Jiang Fan ◽  
John Boscardin ◽  
John L. Fahey

ABSTRACT Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV−) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV− and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P < 0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-α]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV− PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-α mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P < 0.05) and TNF-α (P < 0.005), compared to HIV− PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-α) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.


2015 ◽  
Vol 308 (12) ◽  
pp. R1062-R1069 ◽  
Author(s):  
Jennifer E. Dumaine ◽  
Noah T. Ashley

Sleep deprivation induces acute inflammation and increased glucocorticosteroids in vertebrates, but effects from fragmented, or intermittent, sleep are poorly understood. Considering the latter is more representative of sleep apnea in humans, we investigated changes in proinflammatory (IL-1β, TNF-α) and anti-inflammatory (TGF-β1) cytokine gene expression in the periphery (liver, spleen, fat, and heart) and brain (hypothalamus, prefrontal cortex, and hippocampus) of a murine model exposed to varying intensities of sleep fragmentation (SF). Additionally, serum corticosterone was assessed. Sleep was disrupted in male C57BL/6J mice using an automated sleep fragmentation chamber that moves a sweeping bar at specified intervals (Lafayette Industries). Mice were exposed to bar sweeps every 20 s (high sleep fragmentation, HSF), 120 s (low sleep fragmentation, LSF), or the bar remained stationary (control). Trunk blood and tissue samples were collected after 24 h of SF. We predicted that HSF mice would exhibit increased proinflammatory expression, decreased anti-inflammatory expression, and elevated stress hormones in relation to LSF and controls. SF significantly elevated IL-1β gene expression in adipose tissue, heart (HSF only), and hypothalamus (LSF only) relative to controls. SF did not increase TNF-α expression in any of the tissues measured. HSF increased TGF-β1 expression in the hypothalamus and hippocampus relative to other groups. Serum corticosterone concentration was significantly different among groups, with HSF mice exhibiting the highest, LSF intermediate, and controls with the lowest concentration. This indicates that 24 h of SF is a potent inducer of inflammation and stress hormones in the periphery, but leads to upregulation of anti-inflammatory cytokines in the brain.


2015 ◽  
Vol 35 (5) ◽  
pp. 396-402 ◽  
Author(s):  
David G.G. Schwarz ◽  
Pricila A.G. Pietralonga ◽  
Marina C.C. Souza ◽  
Isabel A. Carvalho ◽  
Rosyane S. Cruzeiro ◽  
...  

AbstractMycobacterium avium subspecies paratuberculosis (MAP) can infect ruminants and remain subclinical for long periods within herds. The identification of organs that are more susceptible to infection and the evaluation of cytokine expression at the site of infection are important to understand the pathogenesis of MAP. In this study, the probability of detection of MAP-DNA and the expression of cytokines in organs of C57BL/6 mice infected intraperitoneally for 120 days were evaluated. Among the evaluated organs, the spleen (85%), colon (75%) and liver (60%) had the highest frequency of positivity. When compared these frequencies between organs, it has been found that the spleen had 1.54 times as likely to be positive in relation to the ileum, and 2.0 times more likely in relation to the Peyer's patches. In addition, at 60 days post-infection, the spleen and the liver were responsible for upregulation of IFN-γ , and the ileum by TNF-α and IL-4. The results indicate that the spleen is the best organ for evaluating an experimental infection by MAP, especially in the initial stages of the infection. Moreover, it showed that the spleen, liver and ileum have a direct role in the inflammatory response in experimental models.


1993 ◽  
Vol 177 (3) ◽  
pp. 863-868 ◽  
Author(s):  
S Miyake ◽  
H Yagita ◽  
T Maruyama ◽  
H Hashimoto ◽  
N Miyasaka ◽  
...  

Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA), whereas the mechanisms for constitutive production of inflammatory cytokines in affected joints are largely unknown. Recently, integrin-mediated interaction with extracellular matrix (ECM) proteins has been demonstrated to play a role in regulating cytokine production in T cells and monocytes. In this study, we investigated the contribution of the beta 1 integrin-mediated interaction with ECM proteins to the persistent cytokine gene expression in RA synovial fluid mononuclear cells (SFMNC). We examined mRNA expression of 14 cytokines in the SFMNC of three RA patients, which were either fresh or cultured overnight in serum-free medium on ECM-coated plates, by polymerase chain reaction with a panel of oligonucleotide primers specific for each cytokine. The persistent expression of various cytokine mRNA found in fresh SFMNC was maintained after overnight culture in serum-free medium on ECM proteins, especially on laminin (LM), but not on serum albumin. This effect of LM was inhibited by an anti-integrin beta 1 chain (CD29) mAb, as well as by an anti-CD3 mAb, indicating an important role of the beta 1 integrin-mediated interaction with ECM proteins in regulating persistent cytokine gene expression in RA SFMNC, and a key role of T cells in regulating inflammatory monokine production.


2021 ◽  
Vol 8 (10) ◽  
pp. 231
Author(s):  
Benito Avila-Jaime ◽  
Yareellys Ramos-Zayas ◽  
Moisés A. Franco-Molina ◽  
René Alvarado-Avila ◽  
Diana E. Zamora-Avila ◽  
...  

Blood samples were obtained from 16 high-risk heifers; eight were newly arrived from a 40 h road trip (0 days post-arrival (DPA)), whereas the other eight heifers had been in the feedlot at 25 DPA. Both groups were transported from the southeast tropical region of Mexico to a feedlot in the northeast and were sampled on the same day. The complete blood count, blood chemistry, and cytokine gene expression were analyzed. Gene expression was analyzed using specific primers to amplify and quantify the cDNA reverse transcribed from the mRNA transcripts for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2. Higher values for hematocrit (p = 0.029), hemoglobin (p = 0.002), eosinophils (0.029), albumin (p = 0.014), alanine aminotransferase (p = 0.004), bilirubin (p = 0.003), cholesterol (p = 0.014), and cortisol (p = 0.051) were observed in the 0 DPA group than the 25 DPA group. In the electrophoresis of TNF-α amplification products, two non-specific bands were observed in the 0 DPA group. These bands were sequenced, and BLAST analysis suggested that they corresponded to bovine lymphotoxin and have not been reported previously related to stress. The TNF-α expression level was higher (p = 0.001) in the 25 DPA group than the 0 DPA group according to the semi-quantitative expression analysis. This may indicate a persistent inflammatory process that could be related to trauma and disease, which can negatively impact their subsequent health and growth performance. In conclusion, homeostatic disruption was apparent in the 0 DPA heifers, which showed higher cortisol and reductions in TNF-α levels and stress-induced bovine lymphotoxin (SIBL) co-expression.


2021 ◽  
Author(s):  
Maria Iribarne ◽  
David Hyde

Unlike mammals, zebrafish regenerate in response to retinal damage. Because microglia are activated by retinal damage, we investigated their role during regeneration following acute or chronic damage. At three weeks-post-fertilization (wpf), fish exhibiting NMDA-induced acute damage or cone photoreceptor-specific chronic degeneration, the gold rush (gosh) mutant, displayed reactive microglia and Müller glia proliferation. Retinas treated to inhibit the immune response lacked reactive microglia and possessed fewer PCNA-positive cells, while LPS treatment increased microglia and PCNA-labeled cells. NMDA-injured retinas upregulated the expression of il-1β and tnf-α pro-inflammatory cytokine genes, followed by increased expression of il-10 and arg1 anti-inflammatory/remodeling cytokine genes. An early and transiently TNF-α pro-inflammatory microglia population was identified in the NMDA-damaged retina. In contrast, gosh mutant retinas exhibited a mild increase of pro-inflammatory cytokine gene expression concurrently with a greater increased in anti-inflammatory/remodeling cytokine gene expression. Few TNF-α pro-inflammatory microglia were observed in the gosh retina. How inflammation regulates regeneration in zebrafish would provide important clues towards improving the therapeutic strategies for repairing injured mammalian tissues.


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