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OSM induced HGF secretion to a similar extent as IL-1\u03b2 in both a time- and dose-dependent manner. HGF was released in its cleaved mature form, and its secretion was completely inhibited in the presence of cycloheximide, indicating a de novo protein synthesis. OSM in combination with prostaglandin E<jats:sub>2<\/jats:sub>, a powerful HGF inductor, led to an additive effect. OSM and indomethacin in combination further increased HGF secretion. This could be explained, at least in part, by a moderate upregulation of specific OSM receptor \u03b2 mRNA expression through cyclooxygenase inhibition.These results demonstrate that OSM-induced HGF synthesis did not involve a PGE<jats:sub>2<\/jats:sub>pathway. OSM-induced HGF secretion was inhibited by PD-98059 (a specific pharmacological inhibitor of ERK1\/2), SB-203580 (a p38 MAPK inhibitor), and SP-600125 (a JNK inhibitor) by 70, 82, and 100%, respectively, whereas basal HGF secretion was only inhibited by SP-600125 by 30%. Our results demonstrate a specific upregulation of HGF synthesis by OSM, most likely through a MAPK pathway, and support the suggestion that OSM may participate in lung repair through HGF production.<\/jats:p>","DOI":"10.1152\/ajplung.00166.2005","type":"journal-article","created":{"date-parts":[[2006,5,9]],"date-time":"2006-05-09T19:55:32Z","timestamp":1147204532000},"page":"L1097-L1103","source":"Crossref","is-referenced-by-count":19,"title":["HGF synthesis in human lung fibroblasts is regulated by oncostatin 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