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PMID: 1689487 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Transforming growth factor beta 1 regulates production of acute-phase proteins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 4 ·1990-02-00 ·Pages 1491-5

Mackiewicz A, Ganapathi MK, Schultz D, Brabenec A, Weinstein J, Kelley MF, Kushner I

Abstract

We explored the possible role of transforming growth factor beta 1 (TGF-beta), a cytokine that appears to be an important modulator of inflammation and tissue repair, in regulation of human plasma protein synthesis during the acute-phase response. In Hep 3B cells, TGF-beta led to increased secretion of the positive acute-phase proteins alpha 1-protease inhibitor and alpha 1-antichymotrypsin and decreased secretion of the negative acute-phase protein albumin. In Hep G2 cells, after incubation with TGF-beta, the same changes in secretion of alpha 1-protease inhibitor, alpha 1-antichymotrypsin, and albumin were observed, as well as decreased secretion of both the negative acute-phase protein alpha-fetoprotein and the positive acute-phase protein fibrinogen. In addition, TGF-beta modulated the effects of interleukin 6; these cytokines, in combination, were additive in inducing synthesis and secretion of alpha 1-protease inhibitor and alpha 1-antichymotrypsin and in decreasing secretion of albumin and alpha-fetoprotein. TGF-beta inhibited the induction of fibrinogen caused by interleukin 6. The effects on alpha 1-protease inhibitor were confirmed by metabolic labeling in Hep 3B cells and by demonstrating increased accumulation of specific mRNA in Hep G2 cells, and the effects on fibrinogen were confirmed in Hep 3B cells by studies of mRNA for the alpha chain of fibrinogen. TGF-beta had no effect on haptoglobin or alpha 1-acid glycoprotein secretion, either directly or in the presence of interleukin 6, which is capable of inducing these proteins. These studies demonstrate that TGF-beta can affect hepatic synthesis and secretion of a subset of acute-phase proteins, both directly and by modulating the effect of interleukin 6. The affected group of plasma proteins is distinct from those affected by other recognized acute-phase protein-inducing cytokines. These findings support the view that combinations of cytokines mediate the response of the hepatocyte to inflammatory stimuli.

MeSH Terms
Acute-Phase Proteins/biosynthesis,genetics,isolation & purification Carcinoma, Hepatocellular Cell Line Fibrinogen/biosynthesis,genetics Humans Interleukin-6/pharmacology Liver Neoplasms RNA, Messenger/drug effects,genetics Recombinant Proteins/pharmacology Transforming Growth Factors/pharmacology alpha 1-Antitrypsin/biosynthesis,genetics
Chemicals
Acute-Phase Proteins Interleukin-6 RNA, Messenger Recombinant Proteins alpha 1-Antitrypsin Transforming Growth Factors Fibrinogen
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Mackiewicz A
Department of Medicine, Case Western Reserve University, Cleveland, OH 44109.
Ganapathi M K
Schultz D
Brabenec A
Weinstein J
Kelley M F
Kushner I
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.4.1491
Published
1990-02-00
Pages
1491-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC53501
Subset
IM
Grants
NIA NIH HHS · AG-02467 · United States
External Links
PubMed source DOI: 10.1073/pnas.87.4.1491 PMC Full Text View journal details
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