Inhibition of p38 MAPK-dependent bronchial contraction after ozone by corticosteroids

F. Li, M. Zhang, F. Hussain, K. Triantaphyllopoulos, A. R. Clark, P. K. Bhavsar, X. Zhou, K. F. Chung

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

We determined the role of p38 mitogen-activated protein kinase (MAPK) in the increased airway smooth muscle (ASM) contractile responses following ozone and modulation by corticosteroids. Mice were exposed to air or ozone (3 ppm for 3 h) and isometric contractile responses of bronchial rings to acetylcholine (ACh) were measured using a myograph in the presence of p38 MAPK inhibitor, SB239063 (10-6 M) or dexamethasone (10-6 M). Because MAPK phosphatase (MKP)-1 is a negative regulator of p38 MAPK, we also studied these effects in MKP-1-/- mice. Bronchial rings from ozone-exposed wild-type and MKP-1-/- mice showed increased contractile responses, with a leftward shift of the dose - response curve in MKP-1-/- mice. SB239063 inhibited bronchial contraction equally in air- and ozone-exposed C57/BL6 and MKP-1-/- mice. Dexamethasone inhibited ACh-induced bronchial contraction in both air- and ozone-exposed C57/BL6 mice, but not in air- or ozone-exposed MKP-1-/- mice. ACh-stimulated p38 MAPK and heat shock protein (HSP)27 phosphorylation, as measured by Western blotting, and this effect was suppressed by SB239063 in C57/BL6 and MKP-1-/- mice, but not by dexamethasone in either airor ozone-exposed MKP-1-/- mice. p38 MAPK plays a role in maximal ACh-induced isometric contractile responses and increased contractility induced by ozone. Dexamethasone inhibits ACh-induced ASM contraction through phosphorylation of p38 MAPK and HSP27. Copyright

Original languageEnglish
Pages (from-to)933-942
Number of pages10
JournalEuropean Respiratory Journal
Volume37
Issue number4
DOIs
Publication statusPublished - 1 Apr 2011

Keywords

  • Acetylcholine
  • Airway smooth muscle
  • Dexamethasone
  • Heat shock protein 27
  • Mitogen-activated protein kinase phosphatase-1
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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