Expression and function of ghrelin in rheumatoid arthritis

• Published in: Brain, behavior, and immunity Vol. 49; p. e4
• Main Authors: Lowin, T, Mickler, C, Straub, R.H
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2015
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2015.06.035

Activation of the immune system in rheumatoid arthritis (RA) is accompanied by perturbations in energy homeostasis. Pro-inflammatory cytokines lead to metabolic changes which results in increased mortality among RA patients. Ghrelin is a gastric hormone that is secreted in response to nutrient starvation and it is a major regulator of blood glucose levels. Increased production of ghrelin has been linked to anti-inflammatory effects in models of chronic inflammation. In this study we investigated the expression of ghrelin, its receptor GHR-S and activating enzyme GOAT in synovial material in RA under inflammatory and standard conditions. Furthermore effects of ghrelin on production of pro-inflammatory cytokines in synovial fibroblasts from RA are shown. Ghrelin, GHR-S and GOAT were expressed in RA and osteoarthritis (OA) synovial tissue. Incubation of RA and OA synovial fibroblasts with TNF significantly increased GHRS-S and ghrelin protein levels, whereas cortisol in high concentrations (<100 nM) decreased levels of both proteins. When cells were co-stimulated with the GHR-S agonist L-692,585 and TNF, IL-6 and IL-8 levels were increased, while antagonism of GHR-S resulted in decreased cytokine production. Up-regulation of ghrelin and GHR-S in response to pro-inflammatory cytokines in synovial fibroblasts might be a pro-inflammatory signal since this can be considered as an energy demand signal from activated cells. Here, ghrelin might divert glucose and other nutrients to sites of inflammation further fueling tissue destruction in RA.