Human mannose-binding protein gene is regulated by interleukins, dexamethasone and heat shock

Mannose-binding protein (MBP) is a plasma protein synthesized by hepatocytes. MBP, a structural analogue of the complement component C1q, can activate complement via the classical pathway and plays an important role in host defence. Expression of the human MBP gene was studied using the human hepatoma cell line HuH-7. RNA extracted from HuH-7 cells was reverse-transcribed to cDNA, amplified by the polymerase chain reaction and analysed by Southern blot hybridization. MBP mRNA expression in HuH-7 cells was increased by interleukin-6 (IL-6), dexamethasone and heat shock, decreased by interleukin 1 (IL-1), and unaffected by interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta). Gel shift assays demonstrated Sp-1 binding sites in the 5' region of the gene, and formation of specific complexes between DNA and nuclear protein extracted from HuH-7 cells treated with IL-1 or IL-6. Human MBP is an acute-phase protein, and transcription of its gene is enhanced by IL-6, dexamethasone and heat shock but inhibited by IL-1. The actions of the cytokines appear to be mediated by specific transcription factors.