During prolonged inflammation, why does the increased production of prostaglandin E2 (PGE2) in synovial joints paradoxically lead to both pro-inflammatory and anti-inflammatory effects?

💡 Explanation

PGE2 exhibits a biphasic effect because it modulates the expression of different EP receptor subtypes on immune cells and synoviocytes. Upregulation of EP4 receptors leads to increased cAMP production, suppressing further inflammation, therefore a shift to anti-inflammatory responses occurs rather than a continued pro-inflammatory state.

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