Deletion of microsomal prostaglandin E synthase-1 does not alter ozone-induced airway hyper-responsiveness

Miao Wang, Philip R. Cooper, Meiqi Jiang, Hengjiang Zhao, Yiqun Hui, Yubing Yao, Joshua C. Tate, Gautam Damera, John A. Lawson, William F. Jester, Angela Franciska Haczku, Reynold A. Panettieri, Garret A. FitzGerald

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Nonsteroidal anti-inflammatory drugs ameliorate pain and fever by inhibiting cyclooxygenase (COX) and suppressing prostanoid formation. Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes formation of PGE2 from the COX product PGH2 and has emerged as a therapeutic target. Inhibition of mPGES-1, however, renders the PGH2 substrate available for diversion to other PG synthases. To address the possibility that substrate diversion augments formation of PGs that might modulate bronchial tone, we assessed the impact of mPGES-1 deletion in a mouse model of ozone-induced airway hyper-responsiveness. Ozone exposure increased total lung resistance to inhaled methacholine in wild-type mice. Deletion of mPGES-1 had little effect on total lung resistance in either naive or ozone-exposed animals. The carbachol-induced narrowing of luminal diameter in intrapulmonary airways of lung slices from acute ozone-exposed mice was also unaltered by mPGES-1 deletion. Likewise, although concentrations of PGE2 were reduced in bronchoalveolar lavage fluid, whereas 6-keto-PGF, PGD2, and PGF, all were increased, deletion of mPGES-1 failed to influence cell trafficking into the airways of either naive or ozone-exposed animals. Despite biochemical evidence of PGH2 substrate diversion to potential bronchomodulator PGs, deletion of mPGES-1 had little effect on ozone-induced airway inflammation or airway hyper-responsiveness. Pharmacologically targeting mPGES-1 may not predispose patients at risk to airway dysfunction.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
StatePublished - Jul 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine


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