MIC-1 is a novel TGF-β superfamily cytokine associated with macrophage activation

Abstract As part of a study to identify novel genes associated with macrophage activation, we have cloned a new member of the transforming growth factor β (TGF-β) superfamily designated macrophage inhibitory cytokine 1 (MIC-1). MIC-1 is synthesized as a 62-kDa intracellular protein, which, after cleavage by a furin like protease, is secreted as a 25-kDa disulfide-linked dimeric protein. Sequence analysis indicates that it does not cluster within any existing TGF-β families, suggesting it may be the first member of a new grouping within the TGF-β superfamily. Tissue Northern blots show that MIC-1 transcripts are only found abundantly in placenta, although smaller amounts are seen in a limited number of other adult and fetal tissues. MIC-1 is not expressed in resting macrophages but is induced by a number of different activation agents, including phorbol myristate acetate, interleukin 1, tumor necrosis factor α, and macrophage colony-stimulating factor but not by lipopolysaccharide or interferon-γ. We have hypothesized that it may be an autocrine inhibitor of macrophage activation but its major biological role is still uncertain. J. Leukoc. Biol. 65: 2–5; 1999.