Role of the endogenous prostaglandin E2 in human lung fibroblast interleukin-11 production.
Interleukin-11 (IL-11) is known to be a member of the interleukin-6 (IL-6)-type cytokine family. IL-11 is likely to be a major determinant of immune regulation in acute and chronic inflammatory lung diseases, although it is not directly linked with specific disease processes. It has already been shown that although unstimulated human lung fibroblasts did not produce significant amounts of IL-11, the addition of interleukin-1 alpha (IL-1 alpha) and/or transforming growth factor-beta (TGF-beta) stimulated fibroblasts dose-dependently to produce IL-11. Northern blot analysis showed that these stimulators also upregulated IL-11 mRNA expression. As it has been previously reported that IL-1 and TGF-beta stimulate prostaglandin E2 (PGE2) release from lung fibroblasts, we investigate here the role of endogenous PGE2 and the direct effects of the two inhibitors of prostaglandin synthesis, indomethacin and dexamethasone, on IL-11 production by human lung fibroblasts. The addition of indomethacin, a cyclo-oxygenase inhibitor, resulted in significant suppression of IL-11 production and mRNA expression in lung fibroblasts. There was no detectable effect of PGE2 alone on IL-11 levels; however, the suppression of IL-11 production by indomethacin was almost completely reversed by addition of PGE2. In contrast, suppression of IL-11 production by indomenthacin was not reversed by addition of thromboxane B2 and carbocyclic thromboxane A2. In addition, dexamethasone completely suppressed IL-11 production and downregulated IL-11 mRNA. These results suggest that endogenous PGE2 acts as an autocrine stimulus for IL-11 production by human lung fibroblasts activated by IL-1 alpha and TGF-beta.
Matsui
S
S
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Yamashita
N
N
Mino
T
T
Taki
H
H
Sugiyama
E
E
Hayashi
R
R
Maruyama
M
M
Kobayashi
M
M
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D017370:Interleukin-11 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D017370:Interleukin-11; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D015232:Dinoprostone; D007213:Indomethacin