Platelet‐derived growth factor‐induced arachidonic acid release for enhancement of prostaglandin E 2 synthesis in human gingival fibroblasts pretreated with interleukin‐1β

Platelet‐derived growth factor (PDGF) is a biological mediator for connective tissue cells and plays a critical role in a wide variety of physiological and pathological processes. We here investigated the effect of PDGF on arachidonic acid release and prostaglandin E 2 (PGE 2 ) synthesis in human gingival fibroblasts (HGF). PDGF induced arachidonic acid release in a time‐ and dose‐dependent manner, and simultaneously induced a transient increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ), but less provoked PGE 2 release and cyclooxygenase‐2 (COX‐2) mRNA expression. When [Ca 2+ ] i was increased by Ca 2+ ‐mobilizaing reagents, arachidonic acid release was increased. The PDGF‐induced arachidonic acid release and increase in [Ca 2+ ] i were prevented by a tyrosine kinase inhibitor. On the other hand, in the HGF pre‐stimulated with interleukin‐1β (IL‐1β), PDGF clearly increased PGE 2 release. The PDGF‐induced PGE 2 release was inhibited by a tyrosine kinase inhibitor. In the HGF pretreated with IL‐1β, arachidonic acid strongly enhanced PGE 2 release and COX‐2 mRNA expression. These results suggest that PDGF stimulates arachidonic acid release by the increase in [Ca 2+ ] i via tyrosine kinase activation, and which contributes to PGE 2 production via COX‐2 expression in HGF primed with IL‐1β. © 2004 Wiley‐Liss, Inc.