PT  - JOURNAL ARTICLE
AU  - F. Li
AU  - M. Zhang
AU  - F. Hussain
AU  - K. Triantaphyllopoulos
AU  - A.R. Clark
AU  - P.K. Bhavsar
AU  - X. Zhou
AU  - K.F. Chung
TI  - Inhibition of p38 MAPK-dependent bronchial contraction after ozone by corticosteroids
AID  - 10.1183/09031936.00021110
DP  - 2011 Apr 01
TA  - European Respiratory Journal
PG  - 933--942
VI  - 37
IP  - 4
4099  - http://erj.ersjournals.com/content/37/4/933.short
4100  - http://erj.ersjournals.com/content/37/4/933.full
SO  - Eur Respir J2011 Apr 01; 37
AB  - 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 air- or 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.