title: The synergistic induction of cyclooxygenase-2 in lung fibroblasts by angiotensin II and pro-inflammatory cytokines.
abstract: Although we have demonstrated that Angiotensin II (Ang II) signaling plays a role in colon and lung tumorigenesis, the precise mechanisms by which Ang II stimulates tumorigenesis remain unclear. The aim of this study was to investigate the synergistic induction of COX-2 by Ang II and pro-inflammatory cytokines in lung fibroblasts. We also compared the efficiencies of Ang II-dependent COX-2 induction in lung epithelial cells and stromal cells. Ang II induced COX-2 expression in lung fibroblasts in a dose-dependent manner (10(-9) to 10(-7) M) through the Ang II subtype 1 receptor (AT(1)). In addition, Ang II synergistically stimulated the induction of COX-2 by pro-inflammatory cytokines, IL-1beta, or TNF-alpha. Our results indicate that the pro-tumorigenic function of Ang II is attributable, in part, to its strong stimulatory effect of COX-2 expression in lung fibroblasts in which synergistic stimulation with pro-inflammatory cytokines was evident. It is also suggested that the AT(1) receptor in lung fibroblasts may be a rational target for chemoprevention of lung cancer.
authors.affiliation: Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Takaya
authors.initials: T
authors.lastname: Matsuzuka
authors.forename: Kathryn
authors.initials: K
authors.lastname: Miller
authors.forename: Lara
authors.initials: L
authors.lastname: Pickel
authors.forename: Chiyo
authors.initials: C
authors.lastname: Doi
authors.forename: Rie
authors.initials: R
authors.lastname: Ayuzawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tamura
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism; D004790:Enzyme Induction; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D008175:Lung Neoplasms / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D007527:Isoenzymes; D000804:Angiotensin II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone