Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis

Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues equally. The pathogenesis of this degenerative process is not completely understood; however, a low-grade inflammation leading to an imbalance between anabolic and katabolic processes is a well-established factor. The complex network of cytokines regulating these processes and cell communication has a central role in the development and progression of osteoarthritis. Concentrations of both proinflammatory and anti-inflammatory cytokines were found to be altered depending on the osteoarthritis stage and activity. In this review, we analyzed individual cytokines involved in the immune processes with an emphasis on their function in osteoarthritis.

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Mechanisms and Effect of Coptidis Rhizoma on Obesity-Induced Inflammation: In Silico and In Vivo Approaches

International Journal of Molecular Sciences ◽

10.3390/ijms22158075 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8075

Author(s):

Oh-Jun Kwon ◽

Ji-Won Noh ◽

Byung-Cheol Lee

Keyword(s):

Adipose Tissue ◽

Inflammatory Cytokines ◽

Tolerance Test ◽

Control Group ◽

Low Grade ◽

Cytokines And Chemokines ◽

Epididymal Fat ◽

Coptidis Rhizoma ◽

Anti Inflammatory

Obesity is characterized as a chronic, low-grade inflammation state accompanied by the infiltration of immune cells into adipose tissue and higher levels of inflammatory cytokines and chemokines. This study aimed to investigate the mechanisms and effects of Coptidis Rhizoma (CR) on obesity and its associated inflammation. First, we applied a network pharmacology strategy to search the target genes and pathways regulated by CR in obesity. Next, we performed in vivo experiments to confirm the antiobesity and anti-inflammatory effects of CR. Mice were assigned to five groups: normal chow (NC), control (high-fat diet (HFD)), HFD + CR 200 mg/kg, HFD + CR 400 mg/kg, and HFD + metformin 200 mg/kg. After 16 weeks of the experimental period, CR administration significantly reduced the weight of the body, epididymal fat, and liver; it also decreased insulin resistance, as well as the area under the curve of glucose in the oral glucose tolerance test and triglyceride in the oral fat tolerance test. We observed a decrease in adipose tissue macrophages (ATMs) and inflammatory M1 ATMs, as well as an increase in anti-inflammatory M2 ATMs. Gene expression levels of inflammatory cytokines and chemokines, including tumor necrosis factor-α, F4/80, and C-C motif chemokine (CCL)-2, CCL4, and CCL5, were suppressed in adipose tissue in the CR groups than levels in the control group. Additionally, histological analyses suggested decreased fat accumulation in the epididymal fat pad and liver in the CR groups than that in the control group. Taken together, these results suggest that CR has a therapeutic effect on obesity-induced inflammation, and it functions through the inhibition of macrophage-mediated inflammation in adipose tissue.

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Adiponectin receptor agonist AdipoRon ameliorates renal inflammation in diet-induced obese mice and endotoxin-treated human glomeruli ex vivo

Diabetologia ◽

10.1007/s00125-021-05473-9 ◽

2021 ◽

Author(s):

Sonja Lindfors ◽

Zydrune Polianskyte-Prause ◽

Rim Bouslama ◽

Eero Lehtonen ◽

Miia Mannerla ◽

...

Keyword(s):

P38 Mapk ◽

Inflammatory Cytokines ◽

Receptor Agonist ◽

Ex Vivo ◽

Adiponectin Receptor ◽

Low Grade ◽

Renal Inflammation ◽

Anti Inflammatory ◽

And Migration ◽

Low Grade Inflammation

Abstract Aims/hypothesis Chronic low-grade inflammation with local upregulation of proinflammatory molecules plays a role in the progression of obesity-related renal injury. Reduced serum concentration of anti-inflammatory adiponectin may promote chronic inflammation. Here, we investigated the potential anti-inflammatory and renoprotective effects and mechanisms of action of AdipoRon, an adiponectin receptor agonist. Methods Wild-type DBA/2J mice were fed with high-fat diet (HFD) supplemented or not with AdipoRon to model obesity-induced metabolic endotoxaemia and chronic low-grade inflammation and we assessed changes in the glomerular morphology and expression of proinflammatory markers. We also treated human glomeruli ex vivo and human podocytes in vitro with AdipoRon and bacterial lipopolysaccharide (LPS), an endotoxin upregulated in obesity and diabetes, and analysed the secretion of inflammatory cytokines, activation of inflammatory signal transduction pathways, apoptosis and migration. Results In HFD-fed mice, AdipoRon attenuated renal inflammation, as demonstrated by reduced expression of glomerular activated NF-κB p65 subunit (NF-κB-p65) (70%, p < 0.001), TNFα (48%, p < 0.01), IL-1β (51%, p < 0.001) and TGFβ (46%, p < 0.001), renal IL-6 and IL-4 (21% and 20%, p < 0.05), and lowered glomerular F4/80-positive macrophage infiltration (31%, p < 0.001). In addition, AdipoRon ameliorated HFD-induced glomerular hypertrophy (12%, p < 0.001), fibronectin accumulation (50%, p < 0.01) and podocyte loss (12%, p < 0.001), and reduced podocyte foot process effacement (15%, p < 0.001) and thickening of the glomerular basement membrane (18%, p < 0.001). In cultured podocytes, AdipoRon attenuated the LPS-induced activation of the central inflammatory signalling pathways NF-κB-p65, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38-MAPK) (30%, 36% and 22%, respectively, p < 0.001), reduced the secretion of TNFα (32%, p < 0.01), and protected against podocyte apoptosis and migration. In human glomeruli ex vivo, AdipoRon reduced the LPS-induced secretion of inflammatory cytokines IL-1β, IL-18, IL-6 and IL-10. Conclusions/interpretation AdipoRon attenuated the renal expression of proinflammatory cytokines in HFD-fed mice and LPS-stimulated human glomeruli, which apparently contributed to the amelioration of glomerular inflammation and injury. Mechanistically, based on assays on cultured podocytes, AdipoRon reduced LPS-induced activation of the NF-κB-p65, JNK and p38-MAPK pathways, thereby impelling the decrease in apoptosis, migration and secretion of TNFα. We conclude that the activation of the adiponectin receptor by AdipoRon is a potent strategy to attenuate endotoxaemia-associated renal inflammation. Graphical abstract

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Dietary Fiber's Effect on High Sensitivity C-reactive Protein Serum in Sedentary Workers

World Nutrition Journal ◽

10.25220/wnj.v05.i1.0006 ◽

2021 ◽

Vol 5 (1) ◽

pp. 40

Author(s):

Livia Kurniati Saputra ◽

Dian Novita Chandra ◽

Ninik Mudjihartini

Keyword(s):

Body Weight ◽

High Sensitivity ◽

The Body ◽

Low Grade ◽

C Reactive Protein ◽

Reactive Protein ◽

Dietary Fiber Intake ◽

Anti Inflammatory ◽

Low Grade Inflammation ◽

Inflammatory Effect

Low grade inflammation has been recognized of being involved in the pathogenesis of chronic disease pandemic. Individual lifestyle plays a major role in the development of low grade inflammation. Sedentary workers are at risk of low grade inflammation due to the nature of their work. Dietary habit also contributes to inflammatory status in the body. Dietary fiber intake indirectly affects the immune system. It has been hypothesized that fiber has anti-inflammatory effects, both body weight-related and body weight-unrelated This review will focus more on body weight-unrelated anti-inflammatory effect of fiber, especially through fiber’s fermentation metabolites, the short chain fatty acid (SCFA). Its anti-inflammatory effect can be seen by monitoring a biomarker of inflammation in the body, the high sensitivity C-reactive protein (hsCRP). This review’s objective is to cover the mechanisms and role of dietary fiber intake on serum hsCRP level as a marker of low grade inflammation on sedentary workers.

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Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00245.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. E1121-E1130 ◽

Cited By ~ 8

Author(s):

Aneseh Adeshirlarijaney ◽

Jun Zou ◽

Hao Q. Tran ◽

Benoit Chassaing ◽

Andrew T. Gewirtz

Keyword(s):

Metabolic Syndrome ◽

Gut Microbiota ◽

Early Stage ◽

Mechanisms Of Action ◽

Low Grade ◽

Inflammatory Agent ◽

Frontline Treatment ◽

Anti Inflammatory ◽

Low Grade Inflammation

Metformin beneficially impacts several aspects of metabolic syndrome including dysglycemia, obesity, and liver dysfunction, thus making it a widely used frontline treatment for early-stage type 2 diabetes, which is associated with these disorders. Several mechanisms of action for metformin have been proposed, including that it acts as an anti-inflammatory agent, possibly as a result of its impact on intestinal microbiota. In accord with this possibility, we observed herein that, in mice with diet-induced metabolic syndrome, metformin impacts the gut microbiota by preventing its encroachment upon the host, a feature of metabolic syndrome in mice and humans. However, the ability of metformin to beneficially impact metabolic syndrome in mice was not markedly altered by reduction or elimination of gut microbiota, achieved by the use of antibiotics or germfree mice. Although reducing or eliminating microbiota by itself suppressed diet-induced dysglycemia, other features of metabolic syndrome including obesity, hepatic steatosis, and low-grade inflammation remained suppressed by metformin in the presence or absence of gut microbiota. These results support a role for anti-inflammatory activity of metformin, irrespective of gut microbiota, in driving some of the beneficial impacts of this drug on metabolic syndrome.

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A Genetic Score of Predisposition to Low-Grade Inflammation Associated with Obesity May Contribute to Discern Population at Risk for Metabolic Syndrome

Nutrients ◽

10.3390/nu11020298 ◽

2019 ◽

Vol 11 (2) ◽

pp. 298 ◽

Cited By ~ 6

Author(s):

Sebastià Galmés ◽

Margalida Cifre ◽

Andreu Palou ◽

Paula Oliver ◽

Francisca Serra

Keyword(s):

Metabolic Syndrome ◽

At Risk ◽

Ex Vivo ◽

Low Grade ◽

Omega 3 ◽

Genetic Score ◽

Population At Risk ◽

Inflammatory Status ◽

Anti Inflammatory ◽

Low Grade Inflammation

Omega-3 rich diets have been shown to improve inflammatory status. However, in an ex vivo system of human blood cells, the efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulating lipid metabolism and cytokine response is attenuated in overweight subjects and shows high inter-individual variability. This suggests that obesity may be exerting a synergistic effect with genetic background disturbing the anti-inflammatory potential of omega-3 long-chain polyunsaturated fatty acids (PUFA). In the present work, a genetic score aiming to explore the risk associated to low grade inflammation and obesity (LGI-Ob) has been elaborated and assessed as a tool to contribute to discern population at risk for metabolic syndrome. Pro-inflammatory gene expression and cytokine production as a response to omega-3 were associated with LGI-Ob score; and lower anti-inflammatory effect of PUFA was observed in subjects with a high genetic score. Furthermore, overweight/obese individuals showed positive correlation of both plasma C-Reactive Protein and triglyceride/HDLc-index with LGI-Ob; and high LGI-Ob score was associated with greater hypertension (p = 0.047), Type 2 diabetes (p = 0.026), and metabolic risk (p = 0.021). The study shows that genetic variation can influence inflammation and omega-3 response, and that the LGI-Ob score could be a useful tool to classify subjects at inflammatory risk and more prone to suffer metabolic syndrome and associated metabolic disturbances.

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Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/347141 ◽

2012 ◽

Vol 2012 ◽

pp. 1-15 ◽

Cited By ~ 74

Author(s):

Ding-Lei Su ◽

Zhi-Min Lu ◽

Min-Ning Shen ◽

Xia Li ◽

Ling-Yun Sun

Keyword(s):

Complex Network ◽

Inflammatory Cytokines ◽

Immune Cells ◽

Inflammatory Disease ◽

Immune Homeostasis ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

Autoimmune Inflammatory Disease ◽

Anti Inflammatory

SLE is an autoimmune inflammatory disease in which various pro- and anti-inflammatory cytokines, including TGF-β, IL-10, BAFF, IL-6, IFN-α, IFN-γ, IL-17, and IL-23, play crucial pathogenic roles. Virtually, all these cytokines can be generated by both innate and adaptive immune cells and exert different effects depending on specific local microenvironment. They can also interact with each other, forming a complex network to maintain delicate immune homeostasis. In this paper, we elaborate on the abnormal secretion and functions of these cytokines in SLE, analyze their potential pathogenic roles, and probe into the possibility of them being utilized as targets for therapy.

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Mechanisms Mediating Anti-Inflammatory Effects of Delta-Tocotrienol and Tart Cherry Anthocyanins in 3T3-L1 Adipocytes

Nutrients ◽

10.3390/nu12113356 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3356

Author(s):

Lexie Harlan ◽

London T. Mena ◽

Latha Ramalingam ◽

Shasika Jayarathne ◽

Chwan-Li Shen ◽

...

Keyword(s):

Metabolic Diseases ◽

Combined Treatment ◽

Low Grade ◽

Tart Cherry ◽

Metabolic Complications ◽

Inflammatory Protein ◽

Anti Inflammatory ◽

Low Grade Inflammation ◽

Macrophage Inflammatory Protein

Chronic low-grade inflammation is a primary characteristic of obesity and can lead to other metabolic complications including insulin resistance and type 2 diabetes (T2D). Several anti-inflammatory dietary bioactives decrease inflammation that accompanies metabolic diseases. We are specifically interested in delta-tocotrienol, (DT3) an isomer of vitamin E, and tart cherry anthocyanins (TCA), both of which possess individual anti-inflammatory properties. We have previously demonstrated that DT3 and TCA, individually, reduced systemic and adipose tissue inflammation in rodent models of obesity. However, whether these compounds have combinatorial effects has not been determined yet. Hence, we hypothesize that a combined treatment of DT3 and TCA will have great effects in reducing inflammation in adipocytes, and that these effects are mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), a major inflammatory transcription factor. We used 3T3-L1 adipocytes and treated them with 1–5 µM doses of DT3 along with tart cherry containing 18–36 µg anthocyanin/mL, to assess effects on inflammation. Neither DT3 nor TCA, nor their combinations had toxic effects on adipocytes. Furthermore, pro-inflammatory markers interleukin-6 (IL-6) and p-65 (subunit of NFkB) were reduced at the protein level in media collected from adipocytes with both individual and combined treatments. Additionally, other downstream targets of NFkB including macrophage inflammatory protein 2 (Mip2), and Cyclooxygenase-2 (Cox2) were also significantly downregulated (p ≤ 0.05) when treated with individual and combined doses of DT3 and TCA with no additional combinatorial effects. In summary, DT3 and TCA individually, are beneficial in reducing inflammation with no additional combinatorial effects.

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Intracerebral Pro-inflammatory Cytokine Increase in Surgically Evacuated Intracerebral Hemorrhage - an Observational Microdialysis Study

10.21203/rs.3.rs-516589/v1 ◽

2021 ◽

Author(s):

Lovisa Tobieson ◽

Anna Gard ◽

Karsten Ruscher ◽

Niklas Marklund

Keyword(s):

Intracerebral Hemorrhage ◽

Brain Tissue ◽

Inflammatory Cytokines ◽

Inflammatory Mediators ◽

Inflammatory Cytokine ◽

Tissue Injury ◽

Treatment Options ◽

Cerebral Microdialysis ◽

Cytokines And Chemokines ◽

Anti Inflammatory

Abstract Background: Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment. Methods: In this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis (MD) catheters; one in the perihemorrhagic zone (PHZ), and one in non-eloquent cortex (SNX) remote from the ICH. The microdialysate was analysed for energy metabolites (including lactate/pyruvate ratio (LPR) and glucose) and for inflammatory mediators using a multiplex immunoassay of 27 cytokines and chemokines at 6-10 hours, 20-26 hours and 44-50 hours after surgery. Results: Deranged energy metabolic markers suggestive of a metabolic crisis were found in PHZ compared to SNX, persistent throughout the 50 hours. Pro-inflammatory cytokines IL-8, TNF-α, IL-2, IL-1β, IL-6 and IFN-γ, anti-inflammatory cytokine IL-13, IL-4, and VEGF-A were significantly higher in PHZ compared to SNX, most prominent at 20-26 hours following ICH evacuation.Conclusions: Higher levels of pro- and anti-inflammatory cytokines in the perihemorrhagic brain tissue suggests a role for inflammatory mediators involved in secondary injury cascades potentially exacerbating tissue injury, which may constitute a target for future medical interventions.

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An update on inflammatory markers in metabolic syndrome

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20212111 ◽

2021 ◽

Vol 8 (6) ◽

pp. 852

Author(s):

Akshay Prashanth Giri ◽

Lokesh Shanmugam

Keyword(s):

Metabolic Syndrome ◽

Inflammatory Cytokines ◽

Inflammatory Markers ◽

Interleukin 10 ◽

Tnf Alpha ◽

Low Grade ◽

Major Health ◽

Inflammatory State ◽

Anti Inflammatory ◽

Global Threat

Metabolic syndrome is an emerging global threat as a major health burden. It is widely presumed that Metabolic syndrome is associated with a low grade chronic inflammatory phenomenon. This inflammatory state is due to the imbalance between the pro and anti-inflammatory cytokines. Studies have been performed on various inflammatory markers in metabolic syndrome like hsCRP, TNF-alpha, Adiponectin, IL-6, IL-10. Articles were chosen from indexed journals from various search engines. Pro inflammatory cytokines like hsCRP, TNF – alpha, Interleukin -6 were found to be increased and anti-inflammatory cytokines like Interleukin – 10 were reduced in metabolic syndrome.

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