Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-κB/p300 binding in human synovial fibroblasts

Tong, Kwok-Man; Shieh, Dong-Chen; Chen, Chao-Ping; Tzeng, Chung‐Yuh; Wang, Shun-Ping; Huang, Kui-Chou; Chiu, Yung-Cheng; Fong, Yi‐Chin; Tang, Chih‐Hsin

doi:10.1016/j.cellsig.2008.04.003

Cited by 133 publications

(97 citation statements)

References 39 publications

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“…36 Leptin was shown to be an inducer of nitric oxide in chondrocytes 12 and of IL-8 in synovial fibroblasts. 13 In addition, leptin is produced by chondrocytes in OA. 11 Finally, an anti-leptin-based approach was proposed for the treatment of inflammatory and autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, adipogenesis is associated with the production of leptin, an adipokine thought to be proinflammatory in both OA and RA. [10][11][12][13] To that purpose, we searched for the PPARg agonist(s) having anti-inflammatory properties in the presence of TNF-a. Three PPAR-g agonists were tested, namely the synthetic rosiglitazone, the precursor of natural PPAR-g agonist 15d-PGJ2, prostaglandin D2 (PGD2) and the plant hormone, genistein.…”

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confidence: 99%

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Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Relić

Zeddou

Desoroux

et al. 2009

Laboratory Investigation

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It was shown recently that synovial fibroblast transformation into adipocytes reduced the expression of interleukin-6 (IL-6) and IL-8. However, the synovial fibroblast adipogenesis was inhibited in inflammatory conditions induced by the tumor necrosis factor-a (TNF-a). Furthermore, adipogenesis is often accompanied by leptin production, a proinflammatory adipokine in rheumatic diseases. In this study, we tested the phytohormone genistein for adipogenic and anti-inflammatory properties on human synovial fibroblasts. Results showed that genistein was able to transform synovial fibroblasts into adipocytes that expressed perilipin-A and produced adiponectin, but not leptin. Furthermore, genistein enhanced glucocorticoid-mediated synovial fibroblast adipogenesis and, in parallel, downregulated glucocorticoid-induced leptin and leptin receptor. Endogenous and TNF-a-induced expressions of IL-6, IL-8, p38, p65 and C/EBP-b were also downregulated by genistein, showing its anti-inflammatory properties. Peroxisome proliferatoractivated receptor-g (PPAR-g) agonist, rosiglitazone, had a synergic effect on genistein-induced adipogenesis, whereas the non-active tyrosine kinase inhibitor, daidzein, had a significantly inferior adipogenic activity than genistein. The Janus kinase-2 tyrosine kinase inhibitor, AG 490, mimicked the anti-leptin effect of genistein. These results showed that genistein-induced adipogenesis involves PPAR-g induction and tyrosine kinase inhibition. In conclusion, genistein, alone or coupled with glucocorticoids, have both adipogenic and anti-inflammatory effects on synovial fibroblasts.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Relić

Zeddou

Desoroux

et al. 2009

Laboratory Investigation

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“…So, in the light of the present results, it is almost difficult to make an unmistakable conclusion about the role of leptin in RA (Bernotiene et al 2006). It is noteworthy that leptin induces IL 8 via leptin receptor, insulin receptor substrate 1, phosphatidylinositol-3-kinase (PI3K), protein kinase B cascade, and promotion of nuclear factor K b (NF-kb)/p300 binding in human synovial fibroblast from RA patients as well as from OA subjects (Tong et al 2008).…”

Section: Leptin: a Mediator Of Immuno-inflammatory Responsementioning

confidence: 99%

Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases

Gómez

Lago²,

Gómez-Reino³

et al. 2009

Journal of Molecular Endocrinology

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The discovery of leptin in 1994 marked the beginning of a new understanding about white adipose tissue (WAT) and modified a static vision of this tissue which was viewed up to the end of the 20th century as an inert tissue, devoted to body protection from heat loss and to passively storing energy. The identification of the product of the gene obese accentuated the role of adipose tissue in the physiopathology of obesity-linked diseases, and led to the discovery of various adipokines, many of a pro-inflammatory nature. It has become progressively manifest that WAT-derived adipokines can now be considered as the fulcrum between obesity-related environmental causes, such as nutrition and lifestyle, and the biochemical shifts that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. Herein, we review recent adipokine research, with particular emphasis to the role of leptin, adiponectin, resistin, and visfatin in chondrocyte function and skeleton, as well as in inflammatory and degenerative cartilage joint diseases.

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“…Together with in vivo experiments, in vitro experiments also revealed a proinflammatory facet of leptin. Leptin increases IL-8 production by RA synovial fibroblast (39) and, in human-cultured chondrocytes, synergizes with IL-1 and interferon-␥ (IFN␥) in the production of nitric oxide (NO) (40,41).…”

Section: Leptin and Rheumatic Diseasesmentioning

confidence: 99%

“…Leptin increases IL-8 production by OA synovial fibroblast (39) and, in human-cultured chondrocytes, synergizes with IL-1 and IFN␥ in the production of NO (40,41). In addition, in human OA chondrocytes, leptin increases MMP-9 and MMP-13 expression (44).…”

Section: Adipokines In Rheumatic Diseases and Cardiovascular Complicamentioning

confidence: 99%

Cardiometabolic comorbidities and rheumatic diseases: Focus on the role of fat mass and adipokines

Lago¹,

Gómez²,

Conde³

et al. 2011

Arthritis Care & Research

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Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-κB/p300 binding in human synovial fibroblasts

Cited by 133 publications

References 39 publications

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases

Cardiometabolic comorbidities and rheumatic diseases: Focus on the role of fat mass and adipokines

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