Prostaglandin H-Synthase-2 Is the Main Enzyme Involved in the Biosynthesis of Octadecanoids from Linoleic Acid in Human Dermal Fibroblasts Stimulated with Interleukin-1β (original) (raw)

1996, Journal of Investigative Dermatology

This study w a s focused on the characterization of the m etabolism of linoleic acid by human dermal fibroblas ts and the effect of interleukin-l on the biosynthesis of octadecanoids. Dermal fibroblasts untreated and tre ated with recombinant IL-lf3 were incubated with exogenous labeled linoleic acid. A combination of high performance liquid chromatography and gas chromatography-mass spectrometry was used as the analytic technique. We found that dermal fibroblasts convert linole ic a cid mainly into 13-hydroxy-9-cis,11trails-octadecadie noic acid (13-HODE) and 9-hydroxy-l 0-tralls,12-cis-octadecadienoic acid (9-HODE), 13(S)-HODE and 9(R)-HODE being the predominant enantiomers. IL-lf3 increased the formation of both 13-HODE and 9-HODE in a concentration-dependent manner with similar EC so values as for prostanoid formation. This effect of IL-lf3 on HODEs formation was concomitant with the expression of prostaglandin L in o leic acid (LA) is an esse nti al CiS-. POIYU. nsa turated fatty ac id and the precursor o f 13-and 9-hydro peroxyoctadecad ienoic (HPODE) acids, w hi ch in turn are redu ced to the corresp o ndin g hyd roxy-octadecadienoic (HODE) acids, th ese being the majo r oxygenated m etabolites of LA p ro du ced by cell s. HPO DEs and H O D Es have bee n fo und in high am o unts in ath eroscleroti c (Kiirm , 1992) and pso riati c lesio ns (Camp cf al.,1 983; Bae r el. ai, 1990, 1991) and have several biologic acti viti es in volved in the inflammatory response (B uchanan el ai, 1985; Yam aj a Se tty el ai, 1987; Iversen et ai , 199 1; K u cl ai, 1992). T he site of oxygen insertion on LA is primarily at the C9 or C 13 and is largely dependen t on th e cell type. In general, enzymatic oxidation

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