Effect of chronic ethanol consumption on the expression of complement components and acute-phase proteins in liver.
The complement system can provoke but also participate in the repair of liver injury. Here we investigated by microarray analysis the effect of chronic ethanol consumption on hepatic mRNA expression of complement components and acute-phase proteins in complement C3-deficient (C3(-/-)) and wild-type (C3(+/+)) mice. Up-regulation by ethanol of factor B, C1qA-chain and clusterin but down-regulation of factor H, Masp-2, factor D and the terminal components C6, C8alpha and C9 was seen in both strains. Ethanol up-regulated C2 and down-regulated C4bp only in C3(+/+) mice, while in C3(-/-) mice up-regulation of C1qB-chain and vitronectin was observed. The expression of factor B, C6, C1qB and factor I was lower but that of factor D higher in C3(-/-) than in C3(+/+) mice. Ethanol induced mRNA synthesis of many acute-phase proteins including SPARC and lipocalin-2, but reduced the expression of SAP. The induction of early classical and alternative pathway components and suppression of terminal pathway components and soluble regulators may thus contribute to alcohol-induced liver injury. Lipocalin-2 and SPARC emerge as new candidate markers for early detection of liver damage.
Bykov
Igor
I
National Public Health Institute, Departments of Mental Health and Alcohol Research, POB 33, 00250 Helsinki, Finland.
Junnikkala
Sami
S
Pekna
Marcela
M
Lindros
Kai O
KO
Meri
Seppo
S
D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000428:Alcohol Drinking / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D003165:Complement System Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D015870:Gene Expression; D000071068:Lipocalin-2; D054834:Lipocalins; D008099:Liver / Q000276:immunology*; D008108:Liver Diseases, Alcoholic / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000276:immunology; D015676:Osteonectin / Q000096:biosynthesis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D015676:Osteonectin; D012333:RNA, Messenger; C071332:Lcn2 protein, mouse; D000431:Ethanol; D003165:Complement System Proteins