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 (IFNα), interferon gamma (IFNγ), interleukin-6 (IL6), interleukin-1 beta (IL1β), monocyte chemotactic factor-1 (MCP1), or tumor necrosis factor alpha (TNFα). 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 IFNα or IL6. One hour of incubation with IFNα or IL6 increased hepcidin mRNA 20 and 80-fold, respectively; by 24 h the mRNA remained 5- and 2.4-fold higher than baseline. IL1β, IFNγ, and MCP-1 did not affect monocyte hepcidin expression. TNFα inhibited hepcidin induction by IL6 in monocytes by 44%. After 24 h of treatment with IFNα or IL6, immunoreactive hepcidin production by monocytes increased 3- and 2.6-fold, respectively.


CONCLUSIONS
Human monocytes produce hepcidin in response to adhesion and the pro-inflammatory cytokines IFNα and IL6.


CONCLUSIONS
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.
Zhang
Xiaolan
X
Department of Internal Medicine, Ohio State University, Columbus, OH, USA.
Rovin
Brad H
BH
D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D018932:Chemokine CCL2 / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D056945:Hep G2 Cells; D064451:Hepcidins; D006801:Humans; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; D018932:Chemokine CCL2; D016207:Cytokines; C578702:HAMP protein, human; D064451:Hepcidins; D018836:Inflammation Mediators; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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