Silswal, N. et al. Human resistin stimulates the pro-inflammatory cytokines TNF- and IL-12 in macrophages by NF-B-dependent pathway. Biochem. Biophys. Res. Commun. 334, 1092-1101

National Institute of Animal Nutrition and Physiology, Bengalūru, Karnataka, India
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 10/2005; 334(4):1092-101. DOI: 10.1016/j.bbrc.2005.06.202
Source: PubMed


Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-alpha and IL-12, similar to that obtained using 5 microg/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-kappaB transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-alpha in U937 cells by hResistin was markedly reduced in the presence of either dominant negative IkappaBalpha plasmid or PDTC, a pharmacological inhibitor of NF-kappaB. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications.


Available from: Nasreen Ehtesham
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    • "It can enhance the expansion of Treg cells through an effect on dendritic cells (Figure 1) [107]. Proinflammatory mediators increase resistin expression; in turn, resistin induces TNF-α, IL-12, IL-6, and IL-1β production [108, 109]. These findings, together with the observation that the intra-articular injection of resistin in the knee joints induces arthritis, sustain the involvement of resistin in RA pathogenesis [110]. "
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    ABSTRACT: Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by severe joint injury. Recently, research has been focusing on the possible identification of predictor markers of disease onset and/or progression, of joint damage, and of therapeutic response. Recent findings have uncovered the role of white adipose tissue as a pleiotropic organ not only specialized in endocrine functions but also able to control multiple physiopathological processes, including inflammation. Adipokines are a family of soluble mediators secreted by white adipose tissue endowed with a wide spectrum of actions. This review will focus on the recent advances on the role of the adipokine network in the pathogenesis of RA. A particular attention will be devoted to the action of these proteins on RA effector cells, and on the possibility to use circulating levels of adipokines as potential biomarkers of disease activity and therapeutic response.
    Mediators of Inflammation 03/2014; 2014:425068. DOI:10.1155/2014/425068 · 3.24 Impact Factor
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    • "These likely represented the resistin trimer and dimer forms (Aruna et al., 2008; Gerber et al., 2005). Since resistin induces cytokine expression via the activation of NF-kB (Silswal et al., 2005), we hypothesized that this activation may be downstream of adenylyl cyclase activation. Though unusual, this order would be consistent with reports of crosstalk between cAMP/PKA signaling and proinflammatory NF-kB pathways in macrophages (Peters-Golden, 2009; Wall et al., 2009). "
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    ABSTRACT: Human resistin is a cytokine that induces low-grade inflammation by stimulating monocytes. Resistin-mediated chronic inflammation can lead to obesity, atherosclerosis, and other cardiometabolic diseases. Nevertheless, the receptor for human resistin has not been clarified. Here, we identified adenylyl cyclase-associated protein 1 (CAP1) as a functional receptor for human resistin and clarified its intracellular signaling pathway to modulate inflammatory action of monocytes. We found that human resistin directly binds to CAP1 in monocytes and upregulates cyclic AMP (cAMP) concentration, protein kinase A (PKA) activity, and NF-κB-related transcription of inflammatory cytokines. Overexpression of CAP1 in monocytes enhanced the resistin-induced increased activity of the cAMP-dependent signaling. Moreover, CAP1-overexpressed monocytes aggravated adipose tissue inflammation in transgenic mice that express human resistin from their monocytes. In contrast, suppression of CAP1 expression abrogated the resistin-mediated inflammatory activity both in vitro and in vivo. Therefore, CAP1 is the bona fide receptor for resistin leading to inflammation in humans.
    Cell metabolism 03/2014; 19(3):484-497. DOI:10.1016/j.cmet.2014.01.013 · 17.57 Impact Factor
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    • "Another evidence linking resistin to inflammation is that plasma resistin levels were found associated with many inflammatory markers in some pathophysiological conditions. Resistin level was also positively associated with levels of inflammatory markers, including soluble TNF-α receptor-2, IL-6, and lipoprotein-associated phospholipase A2 in atherosclerosis patients [43]. "
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    ABSTRACT: Biomarkers are highly specific and sensitive indicators of disease activity. Resistin is a recently discovered adipocytokine, having a potent biomarker quality. Initially resistin was thought to be produced by adipocytes alone; however, emerging evidence suggests that it is also produced in abundance by various cells of the immunoinflammatory system, indicating its role in various chronic inflammatory diseases. Data suggests that resistin plays a role in obesity, insulin resistance, cardiovascular diseases, and periodontitis. Resistin derived its name from the original observation that it induced insulin resistance (resist-in: resist insulin) in mice and is downregulated in mature murine adipocytes cultured in the presence of insulin sensitizing drugs like thiazolidinediones. It is well recognized that obesity, is associated with insulin resistance and diabetes. A three-way relationship has been established between diabetes, obesity and periodontitis. Recent evidence also suggests an association between obesity and increased risk for periodontitis. Our previous research showed incremental elevation of resistin with periodontal disease activity and a reduced level of resistin, after periodontal therapy. Thus resistin would be one of the molecular links connecting obesity, periodontitis, and diabetes and may serve as a marker that links periodontal disease with other systemic diseases. A Medline/PubMed search was carried out for keywords "Diabetes Mellitus," "Periodontitis," and "Resistin," and all relevant research papers from 1990 in English were shortlisted and finalized based on their importance. This review provides an insight into the biological action of resistin and its possible role in periodontitis influenced diabetes mellitus and diabetes induced periodontitis.
    Disease markers 02/2014; 2014(2):930206. DOI:10.1155/2014/930206 · 1.56 Impact Factor
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