title: Autocrine/paracrine induction of tissue inhibitor of metalloproteinase-1 in Chinese hamster ovary cells by oncostatin M.
abstract: Chinese hamster ovary (CHO) cells expressing recombinant human oncostatin M (rOM) were found to secrete high levels of a 28-kDa protein. Sequence analysis of the protein suggested that it was hamster tissue inhibitor of metalloproteinase-1 (TIMP-1). In this study, we show that induction of TIMP-1 mRNA and protein by CHO cells is due to rOM action in an autocrine/paracrine mode. TIMP-1 expression in rOM-producing CHO cells increased concomitantly with methotrexate-induced rOM amplification. TIMP-1 upregulation was not caused by either transfection of nonspecific DNA nor was it a direct effect of treatment of the cells with methotrexate. These results suggest that oncostatin M is a potent inducer of TIMP-1 and that its receptor-mediated expression is conserved across species.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington, USA.
authors.forename: N
authors.initials: N
authors.lastname: Malik
authors.forename: B
authors.initials: B
authors.lastname: Evans
authors.forename: B W
authors.initials: BW
authors.lastname: Greenfield
authors.forename: R A
authors.initials: RA
authors.lastname: Shapiro
authors.forename: M
authors.initials: M
authors.lastname: Hanson
authors.forename: M
authors.initials: M
authors.lastname: Shoyab
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases; D014162:Transfection; D015854:Up-Regulation
chemical_list: D006023:Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D053683:Oncostatin M; D008666:Metalloendopeptidases