ITIH4 Serum Concentration Increases during Acute-Phase Processes in Human Patients and Is Up-Regulated by Interleukin-6 in Hepatocarcinoma HepG2 Cells

• Published in: Biochemical and biophysical research communications Vol. 263; no. 1; pp. 224 - 229
• Main Authors: Piñeiro, Matilde, Alava, Marı́a A., González-Ramón, Nieves, Osada, Jesús, Lasierra, Pilar, Larrad, Luis, Piñeiro, Andrés, Lampreave, Fermı́n
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-09-1999
• Subjects: acute-phase proteins; Acute-Phase Reaction - blood; Adult; Aged; Angina, Unstable - blood; Base Sequence; Calcium-Binding Proteins - biosynthesis; Calcium-Binding Proteins - blood; Calcium-Binding Proteins - genetics; Carcinoma, Hepatocellular - genetics; cytokines; DNA Primers - genetics; Glycoproteins - biosynthesis; Glycoproteins - blood; Glycoproteins - genetics; Haptoglobins - biosynthesis; Haptoglobins - genetics; HepG-2 cells; Humans; IHRP; interleukin-6; Interleukin-6 - pharmacology; ITIH4; Liver Neoplasms - genetics; Male; Middle Aged; Myocardial Infarction - blood; Orosomucoid - biosynthesis; Orosomucoid - genetics; pig-MAP; PK-120; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; RT-PCR; Tumor Cells, Cultured; Up-Regulation - drug effects; ITIH4; PK-120; RT-PCR; cytokines; pig-MAP; acute-phase proteins; HepG-2 cells; interleukin-6; IHRP
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1349

The serum concentration of the inter-α 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 μg/ml to 133 μg/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 35S-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-1β, although up-regulating the expression of α1-acid glycoprotein in these cells, did not induce any effect in the expression of ITIH4. No changes were observed after TNF-α treatments. The results presented here indicate that ITIH4 is a type II acute-phase protein in humans.