ITIH4 serum concentration increases during acute-phase processes in human patients and is up-regulated by interleukin-6 in hepatocarcinoma HepG2 cells.
The serum concentration of the inter-alpha trypsin inhibitor heavy chain 4 protein (ITIH4) increases (from 1.4-3 times) in male patients suffering of different acute-phase processes (myocardial infarction, unstable angina or programmed surgery). The concentration of C-reactive protein (CRP) in these samples ranged from 15 microg/ml to 133 microg/ml. Using the hepatocarcinoma HepG2 cell line we have observed up-regulation of ITIH4 mRNA expression upon dose-response treatments with interleukin-6 (IL-6). This effect correlates with the increase of radiolabeled ITIH4 in the cellular media of (35)S-labeled HepG2 cells treated with the cytokine. A similar effect was observed for haptoglobin mRNA, used as a control for acute-phase protein expression. IL-1beta, although up-regulating the expression of alpha(1)-acid glycoprotein in these cells, did not induce any effect in the expression of ITIH4. No changes were observed after TNF-alpha treatments. The results presented here indicate that ITIH4 is a type II acute-phase protein in humans.
Piñeiro
M
M
Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, E-50009, Spain. pineiro@posta.unizar.es
Alava
M A
MA
González-Ramón
N
N
Osada
J
J
Lasierra
P
P
Larrad
L
L
Piñeiro
A
A
Lampreave
F
F
D000210:Acute-Phase Reaction / Q000097:blood*; D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000097:blood; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D006242:Haptoglobins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D009961:Orosomucoid / Q000096:biosynthesis / Q000235:genetics; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D006023:Glycoproteins; D006242:Haptoglobins; D015850:Interleukin-6; C112970:Itih4 protein, mouse; D009961:Orosomucoid; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; D012334:RNA, Neoplasm