Inflammation, Vol. 18, No. 3, 1994 INTERFERON-ALPHA INHIBITS MURINE MACROPHAGE TRANSFORMING GROWTH FACTOR-BETA mRNA EXPRESSION 1 SHAWKAT DHANANI, MIN HUANG, JIANYI WANG, AND STEVEN M. DUBINETT Division of Pulmonary and Critical Care Medicine UCLA School of Medicine and West Los Angeles VA Medical Center Los Angeles, California 90073 Abstract--Transforming growth factor-beta (TGF-t3), a multifunctional polypeptide is produced by a wide variety of ceils and regulates a broad array of physiological and pathological functions. TGF-/3appears to play a central role in pulmonary fibrosis and may contribute to tumor-associated immunosuppression. Alveolar macrophages are a rich source of TGF-/3 and are intimately involved in lung inflammation. We therefore chose to study TGF-/3 regulation in murine alveolar macrophages as well as an immortalized peritoneal macrophage cell line (IC-21). Murine macrophages were incubated with cytokines to evaluate their role in regulating TGF-B mRNA expression. We conclude that IFN-a downregulates TGF-/3 mRNA expression in murine macrophages. INTRODUCTION Transforming growth factor-beta (TGF-~), a 25-kDa disulfide-linked homodi- mer, belongs to a large superfamily of growth regulatory peptides that is highly conserved throughout evolution (1). It is produced by a wide variety of cells including platelets (2), lymphocytes (3), macrophages (4), and fibroblasts (5), and interacts with specific cell membrane receptors (6) that are found on virtually all cells (7). It is a multifunctional tissue regulator involved in a number of physiological and pathologic processes. In addition, it is known to be an impor- tant regulator of extracellular matrix synthesis and degradation (8-11). Its ubiq- 1This work was supported by the Tobacco-related Disease Research Program (#1KT110), the Uni- versity of California Cancer Research Coordinating Committee, the Jonsson Cancer Center Foun- dation and Veterans Administration Merit Review Research Funds. Min Huang was supported by a Jaye Haddad/Concem Foundation Tumor Immunology fellowship. 301 0360-3997/94/06004)301507.00/0 9 1994 Plenum Publishing Corporation