Role of Prostaglandins, Interleukin-1, Interferon-γ and Anti-Inflammatory Compounds in the Regulation of Thymocyte Proliferation

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 μM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 μM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1β, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

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Anti-Inflammatory Cytokines: Important Immunoregulatory Factors Contributing to Chemotherapy-Induced Gastrointestinal Mucositis

Chemotherapy Research and Practice ◽

10.1155/2012/490804 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 27

Author(s):

Masooma Sultani ◽

Andrea M. Stringer ◽

Joanne M. Bowen ◽

Rachel J. Gibson

Keyword(s):

Inflammatory Cytokines ◽

Proinflammatory Cytokines ◽

Molecular Mechanisms ◽

Tissue Injury ◽

Financial Burden ◽

Interleukin 1 ◽

Treatment Strategies ◽

Inflammatory Reactions ◽

Anti Inflammatory

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.

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Anti-Inflammatory and Antinociceptive Activities of Anthraquinone-2-Carboxylic Acid

Mediators of Inflammation ◽

10.1155/2016/1903849 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 14

Author(s):

Jae Gwang Park ◽

Seung Cheol Kim ◽

Yun Hwan Kim ◽

Woo Seok Yang ◽

Yong Kim ◽

...

Keyword(s):

Carboxylic Acid ◽

Molecular Mechanisms ◽

Interleukin 1 ◽

Nuclear Factor ◽

Experimental Conditions ◽

Gene Assay ◽

Anti Inflammatory ◽

Gastric Irritation

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, thein vivoanti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-)κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive componentsin vivo, thus contributing to the immune regulatory role of fruits and herbs.

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Inhibitory Effect of Mechanical Load on IL-1 Induced Cartilage Degradation Is Mediated by Interferon-Gamma and IL-1 Receptor 1

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-193230 ◽

2008 ◽

Cited By ~ 1

Author(s):

C. T. Chen ◽

S. Park ◽

M. Bhargava ◽

P. A. Torzilli

Keyword(s):

Mechanical Load ◽

Interleukin 1 ◽

Cartilage Degradation ◽

Inhibitory Effect ◽

Interferon Γ ◽

Cytokine Signaling ◽

Matrix Remodeling ◽

Inhibitory Protein ◽

Anti Inflammatory ◽

Related Proteins

Matrix remodeling in articular cartilage is regulated by the elevation and activation of aggrecanases (ADAMTS-4 and ADAMTS-5) and matrix metalloproteinases (MMPs) [2–4, 7–9, 10]. Several recent studies from our and other groups have shown that mechanical loading can counteract interleukin 1 (IL-1) induced pro-inflammatory and catabolic events by down-regulating aggrecanases, MMPs, and pro-inflammatory genes [1, 3, 5, 6], but the molecular mechanism is not clear. Many previous studies have shown that the regulation of pro-inflammatory effect of IL-1 come from several aspects: anti-inflammatory cytokines (TGF-β, IL-10, IL-6 and interferon γ), IL-1 receptor related proteins (IL-1R1, IL-1R2, and IL-1Ra) as well as a family of intracellular inhibitory protein called Suppressor Of Cytokine Signaling (SOCS.) SOCS1 and SOCS3 are especially important, since they can inhibit both MAPK and NF-κB pathways induced by IL-1 [12]. The objective of this study was to determine whether mechanical load affected anti-inflammatory mediators along with anti-catabolic events.

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Interleukin-36 family as a novel regulator of inflammation in the barrier tissues

Medical Immunology (Russia) ◽

10.15789/1563-0625-ifa-1880 ◽

2020 ◽

Vol 22 (1) ◽

pp. 49-60

Author(s):

S. V. Sennikova ◽

A. P. Toptygina

Keyword(s):

Lupus Erythematosus ◽

Skin Diseases ◽

Interleukin 1 ◽

Experimental Studies ◽

Cathepsin G ◽

Special Role ◽

Immune Recognition ◽

Anti Inflammatory ◽

Barrier Tissues

The interleukin-36 (IL-36) family was discerned in the superfamily of interleukin-1 (IL-1) ten years ago. This family includes three isoforms of IL-36α, IL-36β, IL-36γ, which have pro-inflammatory activity and a specific receptor antagonist, IL-36ra, which implements anti-inflammatory function. All of them bind to the same IL-1R6 receptor. The pro-inflammatory isoforms also involve an accessory IL-1RAcP protein into signaling; resulting into conduction of a signal into the cell via the assembling heterodimer receptor. In contrast, IL-36ra inhibits the formation of a heterodimer and blocks the signal transmission. The cytokines of the IL-36 family and appropriate receptors are normally expressed on epithelial cells in barrier tissues such as the respiratory, intestinal tract and skin. Like all cytokines of the IL-1 superfamily, IL-36 is synthesized as inactive form and requires activation, but not due to caspases, but being mediated by neutrophil enzymes, such as cathepsin G, proteinase-3, and elastase, which are constantly present in barrier tissues. In this regard, IL-36 is involved in homeostasis of barrier tissues. Apparently, the IL-36 cytokine system appeared in response to the developing ability of some microorganisms to avoid immune recognition and activation of innate immune response, and, in particular, the IL-1 pro-inflammatory system. An imbalance between the pro- and anti-inflammatory pathways readily causes inflammation in the corresponding tissue. This review discusses participation of cytokines from the IL-36 family in homeostasis of barrier tissues, as well as potential role of the IL-36 family in pathogenesis of bacterial, viral, and fungal skin diseases, atopic dermatitis, autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, ulcerative colitis and Crohn's disease. The role of IL-36 family cytokines in the immunopathogenesis of psoriasis has been well studied. This review is presenting the modern ideas about immune pathogenesis of psoriasis. The special role of cytokines from the IL-36 family was shown both for induction of psoriatic inflammation and evolving a positive feedback loop that supports and enhances the immune component of inflammation, which leads to progression of the disease. Moreover, modern methods of treating psoriasis are discussed, in particular, a possible promising approach to IL-36 blockade, or usage of recombinant IL-36ra for the treatment of psoriatic patients. Experimental studies in this area in mice provide some grounds for optimism.

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