Autocrine/paracrine induction of tissue inhibitor of metalloproteinase-1 in Chinese hamster ovary cells by oncostatin M.
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.
Malik
N
N
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington, USA.
Evans
B
B
Greenfield
B W
BW
Shapiro
R A
RA
Hanson
M
M
Shoyab
M
M
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
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