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 language | English |
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Pages (from-to) | 933-942 |
Number of pages | 10 |
Journal | European Respiratory Journal |
Volume | 37 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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