Hepcidin expression by human monocytes in response to adhesion and pro-inflammatory cytokines

Background: A previous urine proteomic analysis from our laboratory suggested that hepcidin may be a biomarker for lupus nephritis flare. Immunohistochemical staining of kidney biopsies from lupus patients showed that hepcidin was expressed by infiltrating renal leukocytes. Here we investigated whether inflammatory cytokines relevant to the pathogenesis of lupus nephritis and other glomerular diseases regulate hepcidin expression by human monocytes. Methods: Human CD14+ monocytes were incubated with interferon alpha (IFN alpha), interferon gamma (IFN gamma), interleukin-6 (IL6), interleukin-1 beta (IL1 beta), monocyte chemotactic factor-1 (MCP1), or tumor necrosis factor alpha (TNF alpha). Hepcidin expression was examined by real-time PCR and enzyme immunoassay. Results: Monocyte hepcidin mRNA increased during adherence to the tissue culture wells, reaching a level 150-fold higher than baseline within 12 h of plating. After accounting for the effects of adhesion, monocytes showed time and dose-dependent up-regulation of hepcidin mRNA upon treatment with IFN alpha or IL6. One hour of incubation with IFN alpha or 16 increased hepcidin mRNA 20 and 80-fold, respectively: by 24 h the mRNA remained 5- and 2.4-fold higher than baseline. IL1 beta. IFN gamma, and MCP-1 did not affect monocyte hepcidin expression. TNF alpha inhibited hepcidin induction by IL6 in monocytes by 44%. After 24 h of treatment with IFN alpha or IL6, immunoreactive hepcidin production by monocytes increased 3- and 2.6-fold, respectively. Conclusion: Human monocytes produce hepcidin in response to adhesion and the pro-inflammatory cytokines IFN alpha. and IL6. General significance: The appearance of hepcidin in the kidneys or urine during glomerular diseases may be from infiltrating monocytes induced to express hepcidin by adherence and exposure to pro-inflammatory cytokines found in the renal milieu. (C) 2010 Elsevier B.V. All rights reserved.