title: MIC-1 is a novel TGF-beta 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 beta (TGF-beta) 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-beta families, suggesting it may be 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 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 alpha, and macrophage colony-stimulating factor but not by lipopolysaccharide or interferon-gamma. We have hypothesized that it may be an autocrine inhibitor of macrophage activation but its major biological role is still uncertain.
authors.affiliation: Centre for Immunology, St Vincent's Hospital and University of New South Wales, Sydney, Australia.
authors.forename: W D
authors.initials: WD
authors.lastname: Fairlie
authors.forename: A G
authors.initials: AG
authors.lastname: Moore
authors.forename: A R
authors.initials: AR
authors.lastname: Bauskin
authors.forename: P K
authors.initials: PK
authors.lastname: Russell
authors.forename: H P
authors.initials: HP
authors.lastname: Zhang
authors.forename: S N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D055436:Growth Differentiation Factor 15; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D016207:Cytokines; D018076:DNA, Complementary; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D016212:Transforming Growth Factor beta