Platelet-derived growth factor-induced arachidonic acid release for enhancement of prostaglandin E2 synthesis in human gingival fibroblasts pretreated with interleukin-1?

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Abstract
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 E2 (PGE2) 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 Ca2+ concentration ([Ca2+]i), but less provoked PGE2 release and cyclooxygenase‐2 (COX‐2) mRNA expression. When [Ca2+]i was increased by Ca2+‐mobilizaing reagents, arachidonic acid release was increased. The PDGF‐induced arachidonic acid release and increase in [Ca2+]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 PGE2 release. The PDGF‐induced PGE2 release was inhibited by a tyrosine kinase inhibitor. In the HGF pretreated with IL‐1β, arachidonic acid strongly enhanced PGE2 release and COX‐2 mRNA expression. These results suggest that PDGF stimulates arachidonic acid release by the increase in [Ca2+]i via tyrosine kinase activation, and which contributes to PGE2 production via COX‐2 expression in HGF primed with IL‐1β.

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