Transforming growth factor-beta induces collagen synthesis without inducing IL-8 production in mesothelial cells.

Lee YC, Lane KB, Zoia O, Thompson PJ, Light RW, Blackwell TS
Eur Respir J. 2003 22 (2): 197-202

PMID: 12952247 · DOI:10.1183/09031936.03.00086202

Conventional pleurodesing agents often provoke acute pleural inflammation followed by fibrosis. The inflammation frequently causes pain and fever. Transforming growth factor (TGF)-beta is a pro-fibrotic but anti-inflammatory cytokine. Intrapleural TGF-beta2 administration produces effective pleurodesis in animals, but its effects on mesothelial cells are unknown. The authors hypothesised that, unlike conventional pleurodesing agents, TGF-beta2 can induce collagen synthesis without stimulating pleural inflammation. In the in vitro studies, TGF-beta2, talc and doxycycline were administered to rabbit mesothelial cells for 24 h. These agents were also injected intrapleurally in rabbits and the induced pleural fluids collected at 24 h. TGF-beta2 was as potent as talc and doxycycline in upregulating mesothelial cell collagen expression. Talc and doxycycline both induced significant increases in interleukin (IL)-8 production from mesothelial cells in vitro and in rabbit pleural fluids in vivo. TGF-beta2, however, did not stimulate mesothelial cell IL-8 release in vitro and induced a dose-dependent suppression of pleural fluid IL-8. Pleural fluid IL-8 levels correlated significantly with leukocyte and lactate dehydrogenase concentrations in the fluids. In summary, transforming growth factor-beta was a potent inducer of mesothelial cell collagen synthesis. Unlike talc and tetracycline, which provoked pleural inflammation, transforming growth factor-beta2 suppressed pleural inflammation in vivo. Transforming growth factor-beta2 can produce effective pleural fibrosis without necessitating acute pleural inflammation.

MeSH Terms (13)

Animals Anti-Bacterial Agents Cells, Cultured Collagen Dose-Response Relationship, Drug Doxycycline Epithelial Cells Injections Interleukin-8 Pleura Rabbits Talc Transforming Growth Factor beta

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