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

As part of a study to identify novel genes associated with macrophage activ ation, we hare cloned a new member of the transforming growth factor beta ( TGF-beta) superfamily designated macrophage inhibitory cytokine 1 (MIC-1). MIC-1 is synthesized as a 62-kDa intracellular protein, which, after cleava ge by a furin like protease, is secreted as a 25-kDa disulfide-linked dimer ic protein. Sequence analysis indicates that it does not cluster within any existing TGF-beta families, suggesting it may he the first member of a new grouping within the TGF-beta superfamily. Tissue Northern blots show that MIC-1 transcripts are only found abundantly in placenta, although smaller a mounts 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 diff erent activation agents, including phorbol myristate acetate, interleukin I , tumor necrosis factor or, and macrophage colony-stimulating factor but no t by lipopolysaccharide or interferon-gamma, We have hypothesized that it m ay be an autocrine inhibitor of macrophage activation but its major biologi cal role is still uncertain.