AI Article Synopsis

  • * PAR2 stimulation specifically increased the levels of microsomal PGES-1 (mPGES-1) and COX-2, while not affecting the other isozymes, mPGES-2 or cytosolic PGES (cPGES).
  • * The rise in mPGES-1 was inhibited by certain blockers, revealing that it is regulated through a specific pathway involving COX-1 and other proteins, which is essential

Article Abstract

We investigated possible involvement of three isozymes of prostaglandin E synthase (PGES), microsomal PGES-1 (mPGES-1), mPGES-2 and cytosolic PGES (cPGES) in COX-2-dependent prostaglandin E(2) (PGE(2)) formation following proteinase-activated receptor-2 (PAR2) stimulation in human lung epithelial cells. PAR2 stimulation up-regulated mPGES-1 as well as COX-2, but not mPGES-2 or cPGES, leading to PGE(2) formation. The PAR2-triggered up-regulation of mPGES-1 was suppressed by inhibitors of COX-1, cytosolic phospholipase A(2) (cPLA(2)) and MEK, but not COX-2. Finally, a selective inhibitor of mPGES-1 strongly suppressed the PAR2-evoked PGE(2) formation. PAR2 thus appears to trigger specific up-regulation of mPGES-1 that is dependent on prostanoids formed via the MEK/ERK/cPLA(2)/COX-1 pathway, being critical for PGE(2) formation.

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http://dx.doi.org/10.1002/cbf.1434DOI Listing

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