Cytokines and endotoxin induce cytokine receptors in skeletal muscle

2000 ◽  
Vol 279 (1) ◽  
pp. E196-E205 ◽  
Author(s):  
Yan Zhang ◽  
Geneviève Pilon ◽  
André Marette ◽  
Vickie E. Baracos

Proinflammatory cytokines are important factors in the regulation of diverse aspects of skeletal muscle function; however, the muscle cytokine receptors mediating these functions are uncharacterized. Binding kinetics (dissociation constant = 39 ± 4.7 × 10−9M, maximal binding = 3.5 ± 0.23 × 10−12mol/mg membrane protein) of muscle tumor necrosis factor (TNF) receptors were obtained. Skeletal muscle was found to express mRNAs encoding interleukin-1 type I and II receptors, interleukin-6 receptor (IL-6R), and interferon-γ receptor by RT-PCR, but these receptors were below limits of detection of ligand-binding assay (≥1 fmol binding sites/mg protein). Twenty-four hours after intraperitoneal administration of endotoxin to rats, TNF receptor type II (TNFRII) and IL-6R mRNA were increased in skeletal muscle ( P < 0.05). In cultured L6 cells, the expression of mRNA encoding TNFRII and IL-6R receptors was induced by TNF-α, and all six cytokine receptor mRNA were induced by a mixture of TNF-α, IFN-γ, and endotoxin ( P < 0.05). This suggests that the low level of cytokine receptor expression is complemented by a capacity for receptor induction, providing a clear mechanism for amplification of cytokine responses at the muscle level.

2004 ◽  
Vol 287 (6) ◽  
pp. L1186-L1192 ◽  
Author(s):  
Eleonora Cavarra ◽  
Fabio Carraro ◽  
Silvia Fineschi ◽  
Antonella Naldini ◽  
Barbara Bartalesi ◽  
...  

The sensitivity to the fibrosis-inducing effect of bleomycin varies considerably from species to species, the reasons for which are unknown. The variability of the response in different strains of mice is well documented. Recent evidence indicates that the upregulated expression of cytokines and cytokine receptors may be involved. We evaluated the expression pattern of some cytokines and their receptors in C57Bl/6J bleomycin-sensitive and Balb/C bleomycin-resistant mice. Animals from both strains received, under ether anesthesia, either saline (50 μl) or bleomycin (0.1 U/50 μl) intratracheally. At various times after the treatment, the lungs were analyzed for cytokines and cytokine receptors by histochemistry and their mRNA by RNase protection assay. A significantly increased expression of TNF-α and IL-1β was observed in both strains. However, an upregulated lung expression for TNF-α and IL-1 receptors was observed in C57Bl/6J-sensitive animals only. This profile is evident from 63 h onward. In addition to TNF-α, bleomycin administration also resulted in the upregulated expression of TGF-β in the lungs of both strains at 8 h and in an enhanced expression of TGF-β receptors I and II in C57Bl/6J mice only. The upregulation of TGF-β receptor expression was preceded in this strain by an increased expression of IL-4, IL-13, and IL-13 receptor-α (at 8 h after bleomycin) and followed by an upregulation of gp130 and IL-6. The difference we observed in the cytokine receptor profile may offer an additional explanation for the different fibrogenic response of the two mouse strains to bleomycin.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Z. Darabseh ◽  
Thomas M. Maden-Wilkinson ◽  
George Welbourne ◽  
Rob C. I. Wüst ◽  
Nessar Ahmed ◽  
...  

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.


1998 ◽  
Vol 26 (4) ◽  
pp. 598-602 ◽  
Author(s):  
Donald T. Kirkendall ◽  
William E. Garrett

Aging results in a gradual loss of muscle function, and there are predictable age-related alterations in skeletal muscle function. The typical adult will lose muscle mass with age; the loss varies according to sex and the level of muscle activity. At the cellular level, muscles loose both cross-sectional area and fiber numbers, with type II muscle fibers being the most affected by aging. Some denervation of fibers may occur. The combination of these factors leads to an increased percentage of type I fibers in older adults. Metabolically, the glycolytic enzymes seem to be little affected by aging, but the aerobic enzymes appear to decline with age. Aged skeletal muscle produces less force and there is a general “slowing” of the mechanical characteristics of muscle. However, neither reduced muscle demand nor the subsequent loss of function is inevitable with aging. These losses can be minimized or even reversed with training. Endurance training can improve the aerobic capacity of muscle, and resistance training can improve central nervous system recruitment of muscle and increase muscle mass. Therefore, physical activity throughout life is encouraged to prevent much of the age-related impact on skeletal muscle.


2020 ◽  
Vol 15 (5) ◽  
pp. 18-23
Author(s):  
G.P. Evseeva ◽  
◽  
G.N. Kholodok ◽  
S.V. Pichugina ◽  
S.V. Suprun ◽  
...  

Principles of the diagnosis and treatment of community-acquired pneumonia (CAP) in children were developed and clearly formulated long ago. Nevertheless, clinicians often encounter the problem of pulmonary and pleural complications of CAP, which is challenging in terms of the choice of initial therapy, since the first symptoms of uncomplicated and complicated pneumonia are often similar. Therefore, the search for early markers of complicated CAP in children is highly important. Objective. To assess prognostic values of spontaneous and mitogen-induced cytokine production in children with CAP. Patients and methods. We have performed comprehensive examination of 108 children with CAP. Eighty-four of them had uncomplicated CAP, whereas 24 children had CAP complicated by pleurisy. We measured spontaneous and induced production of the following cytokines upon patient admission to hospital: interleukin-1 (IL-1), interleukin-17 (IL-17), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). To measure induced cytokine production, we stimulated peripheral blood lymphocytes by S. рneumonае (serotype 7, 11; strains 7C and 11AD). The level of cytokines was evaluated using the enzyme-linked immunosorbent assay (Vektor-BEST, Novosibirsk, Russia). Results. We found that in children with uncomplicated CAP, induction of immunocompetent blood cells (IBCs) led to increased secretion of first-generation cytokines, including IL-1, TNF-α, and IFN-γ, whereas IBCs of patients with complicated CAP primarily produced second-generation cytokines, including VEGF, МРС-1, and IL-17. Conclusion. The observed differences in spontaneous and mitogen-induced cytokine production between children with and without CAP complications suggest that these parameters can be considered as promising prognostic markers for complicated CAP in children. The proposed method can be used in pediatric practice to predict the development of complications in children with CAP. Key words: children, community-acquired pneumonia, cytokines


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2274
Author(s):  
Roi Cal ◽  
Heidi Davis ◽  
Alish Kerr ◽  
Audrey Wall ◽  
Brendan Molloy ◽  
...  

Skeletal muscle is the metabolic powerhouse of the body, however, dysregulation of the mechanisms involved in skeletal muscle mass maintenance can have devastating effects leading to many metabolic and physiological diseases. The lack of effective solutions makes finding a validated nutritional intervention an urgent unmet medical need. In vitro testing in murine skeletal muscle cells and human macrophages was carried out to determine the effect of a hydrolysate derived from vicia faba (PeptiStrong: NPN_1) against phosphorylated S6, atrophy gene expression, and tumour necrosis factor alpha (TNF-α) secretion, respectively. Finally, the efficacy of NPN_1 on attenuating muscle waste in vivo was assessed in an atrophy murine model. Treatment of NPN_1 significantly increased the phosphorylation of S6, downregulated muscle atrophy related genes, and reduced lipopolysaccharide-induced TNF-α release in vitro. In a disuse atrophy murine model, following 18 days of NPN_1 treatment, mice exhibited a significant attenuation of muscle loss in the soleus muscle and increased the integrated expression of Type I and Type IIa fibres. At the RNA level, a significant upregulation of protein synthesis-related genes was observed in the soleus muscle following NPN_1 treatment. In vitro and preclinical results suggest that NPN_1 is an effective bioactive ingredient with great potential to prolong muscle health.


1997 ◽  
Vol 56 (6) ◽  
pp. 1513-1526 ◽  
Author(s):  
Edith Gomez ◽  
Gérard Morel ◽  
Annie Cavalier ◽  
Marie-Odile Liénard ◽  
France Haour ◽  
...  

2010 ◽  
Vol 298 (3) ◽  
pp. R790-R798 ◽  
Author(s):  
Joseph G. Cannon ◽  
Miriam Cortez-Cooper ◽  
Eric Meaders ◽  
Judith Stallings ◽  
Sara Haddow ◽  
...  

Recent studies have indicated that follicle-stimulating hormone (FSH) promotes bone loss. The present study tested the hypothesis that FSH enhances the activity of bone-resorbing cytokines [interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6], either by inducing their secretion or by altering their receptor expression. Thirty-six women between the ages of 20 and 50 were assessed for bone mineral density (BMD), reproductive hormone, cytokine ligand and soluble receptor concentrations, and surface expression of cytokine receptors on monocytes. In addition, isolated mononuclear cells were incubated in vitro with exogenous FSH. Univariate regression analyses indicated that BMD was inversely related to serum FSH ( r = −0.29 to −0.51, P = 0.03–0.001, depending upon the skeletal site). Physical activity and body composition were also identified as significant factors by multiple regressions. Exogenous FSH induced isolated cells to secrete IL-1β, TNF-α, and IL-6 in proportion to the surface expression of FSH receptors on the monocytes. Endogenous (serum) FSH concentrations correlated with the circulating concentrations of these cytokines. None of these individual cytokines was related to BMD, but the IL-1β to IL-1 receptor antagonist (IL-1Ra) ratio was inversely related to BMD ( r = −0.53, P = 0.002) in all but the most physically active women, who had significantly lower expression of IL-1 type I receptors relative to type II (decoy receptors, P = 0.01). Physical activity also correlated positively with secretion of inhibitory soluble IL-1 receptors ( r = 0.53, P = 0.003). Moreover, IL-1Ra correlated strongly with percent body fat ( r = 0.66, P < 0.0001). These results indicate that BMD is related to FSH concentration, physical activity, and body composition. Although each of these factors likely has direct effects on bone, the present study suggests that each may also influence BMD by modulating the activity of the osteoresorptive cytokine IL-1β.


2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Kechun Tang ◽  
George Murano ◽  
Peter D. Wagner ◽  
Ellen C. Breen

2017 ◽  
Vol 76 (12) ◽  
pp. 2075-2084 ◽  
Author(s):  
Wen-Xiu Mo ◽  
Shan-Shan Yin ◽  
Hua Chen ◽  
Chen Zhou ◽  
Jia-Xin Zhou ◽  
...  

ObjectivesTo explore the role of Vδ2 T cells in the pathogenesis of rheumatoid arthritis (RA).MethodsSixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled in the study. All patients with RA fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA. Peripheral Vδ2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of Vδ2 T cells within the synovium was examined by immunohistochemistry and flow cytometry. The effect of tumour necrosis factor (TNF)-α and interleukin (IL)-6 on Vδ2 T migration was determined by flow cytometry and transwell migration assay.ResultsPeripheral Vδ2T cells, but not Vδ1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. Vδ2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-γ and IL-17. Phenotypically, Vδ2 T cells from RA showed elevated chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-α through nuclear factor kappa B signalling. In vivo, TNF-α neutralising therapy dramatically downregulated CCR5 and CXCR3 on Vδ2 T cells and repopulated the peripheral Vδ2 T cells in patients with RA.ConclusionsHigh levels of TNF-α promoted CCR5 and CXCR3 expression in Vδ2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting Vδ2 T cells might be a potential approach for RA.


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