Inhibition of P38 MAPK-dependent Bronchial Contraction After Ozone by Corticosteroids

Overview

Journal Eur Respir J

Specialty Pulmonary Medicine

Date 2010 Aug 10

PMID 20693246

Citations 19

Authors

F Li

M Zhang

F Hussain

K Triantaphyllopoulos

A R Clark

P K Bhavsar

X Zhou

K F Chung

Affiliations

Soon will be listed here.

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 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.

Citing Articles

RNA-seq profiling of tubulointerstitial tissue reveals a potential therapeutic role of dual anti-phosphatase 1 in glomerulonephritis.

Park S, Lee H, Lee J, Lee S, Cho S, Huh H J Cell Mol Med. 2022; 26(12):3364-3377.

PMID: 35488446 PMC: 9189340. DOI: 10.1111/jcmm.17340.

Oxidative Stress in Ozone-Induced Chronic Lung Inflammation and Emphysema: A Facet of Chronic Obstructive Pulmonary Disease.

Wiegman C, Li F, Ryffel B, Togbe D, Chung K Front Immunol. 2020; 11:1957.

PMID: 32983127 PMC: 7492639. DOI: 10.3389/fimmu.2020.01957.

Acute Respiratory Barrier Disruption by Ozone Exposure in Mice.

Sokolowska M, Quesniaux V, Akdis C, Chung K, Ryffel B, Togbe D Front Immunol. 2019; 10:2169.

PMID: 31608051 PMC: 6758598. DOI: 10.3389/fimmu.2019.02169.

Role of Dual-Specificity Phosphatase 1 in Glucocorticoid-Driven Anti-inflammatory Responses.

Hoppstadter J, Ammit A Front Immunol. 2019; 10:1446.

PMID: 31316508 PMC: 6611420. DOI: 10.3389/fimmu.2019.01446.

Sustained exposure to prostaglandin D augments the contraction induced by acetylcholine via a DP receptor-mediated activation of p38 in bronchial smooth muscle of naive mice.

Suto W, Sakai H, Chiba Y J Smooth Muscle Res. 2019; 55(0):1-13.

PMID: 30918168 PMC: 6433600. DOI: 10.1540/jsmr.55.1.

References

Amrani Y, Martinet N, Bronner C . Potentiation by tumour necrosis factor-alpha of calcium signals induced by bradykinin and carbachol in human tracheal smooth muscle cells. Br J Pharmacol. 1995; 114(1):4-5. PMC: 1510165. DOI: 10.1111/j.1476-5381.1995.tb14896.x. View

Frantz B, Klatt T, Pang M, Parsons J, Rolando A, Williams H . The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding. Biochemistry. 1998; 37(39):13846-53. DOI: 10.1021/bi980832y. View

Issa R, Xie S, Khorasani N, Sukkar M, Adcock I, Lee K . Corticosteroid inhibition of growth-related oncogene protein-alpha via mitogen-activated kinase phosphatase-1 in airway smooth muscle cells. J Immunol. 2007; 178(11):7366-75. DOI: 10.4049/jimmunol.178.11.7366. View

Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch R . MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha. Science. 2002; 295(5558):1291-4. DOI: 10.1126/science.1067289. View

Galan A, Garcia-Bermejo M, Troyano A, Vilaboa N, de Blas E, Kazanietz M . Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells. J Biol Chem. 2001; 275(15):11418-24. DOI: 10.1074/jbc.275.15.11418. View

Adcock I, Chung K, Caramori G, Ito K . Kinase inhibitors and airway inflammation. Eur J Pharmacol. 2006; 533(1-3):118-32. DOI: 10.1016/j.ejphar.2005.12.054. View

Goncharova E, Vorotnikov A, Gracheva E, Wang C, Panettieri Jr R, Stepanova V . Activation of p38 MAP-kinase and caldesmon phosphorylation are essential for urokinase-induced human smooth muscle cell migration. Biol Chem. 2002; 383(1):115-26. DOI: 10.1515/BC.2002.012. View

Williams A, Issa R, Durham A, Leung S, Kapoun A, Medicherla S . Role of p38 mitogen-activated protein kinase in ozone-induced airway hyperresponsiveness and inflammation. Eur J Pharmacol. 2008; 600(1-3):117-22. DOI: 10.1016/j.ejphar.2008.09.031. View

Gerthoffer W, Singer C . MAPK regulation of gene expression in airway smooth muscle. Respir Physiol Neurobiol. 2003; 137(2-3):237-50. DOI: 10.1016/s1569-9048(03)00150-2. View

10.

Bitar K . HSP27 phosphorylation and interaction with actin-myosin in smooth muscle contraction. Am J Physiol Gastrointest Liver Physiol. 2002; 282(5):G894-903. DOI: 10.1152/ajpgi.00141.2001. View

11.

Yamboliev I, Hedges J, Mutnick J, Adam L, Gerthoffer W . Evidence for modulation of smooth muscle force by the p38 MAP kinase/HSP27 pathway. Am J Physiol Heart Circ Physiol. 2000; 278(6):H1899-907. DOI: 10.1152/ajpheart.2000.278.6.H1899. View

12.

Mourey R, Burnette B, Brustkern S, Daniels J, Hirsch J, Hood W . A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010; 333(3):797-807. DOI: 10.1124/jpet.110.166173. View

13.

Kumar S, Boehm J, Lee J . p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov. 2003; 2(9):717-26. DOI: 10.1038/nrd1177. View

14.

Gaestel M, Mengel A, Bothe U, Asadullah K . Protein kinases as small molecule inhibitor targets in inflammation. Curr Med Chem. 2007; 14(21):2214-34. DOI: 10.2174/092986707781696636. View

15.

Nabishah B, Morat P, Kadir B, Khalid B . Effect of steroid hormones on muscarinic receptors of bronchial smooth muscle. Gen Pharmacol. 1991; 22(2):389-92. DOI: 10.1016/0306-3623(91)90469-m. View

16.

Mirzapoiazova T, Kolosova I, Romer L, Garcia J, Verin A . The role of caldesmon in the regulation of endothelial cytoskeleton and migration. J Cell Physiol. 2004; 203(3):520-8. DOI: 10.1002/jcp.20244. View

17.

Diskin R, Askari N, Capone R, Engelberg D, Livnah O . Active mutants of the human p38alpha mitogen-activated protein kinase. J Biol Chem. 2004; 279(45):47040-9. DOI: 10.1074/jbc.M404595200. View

18.

Jones G, OByrne P, Pashley M, Serio R, Jury J, LANE C . Airway smooth muscle responsiveness from dogs with airway hyperresponsiveness after O3 inhalation. J Appl Physiol (1985). 1988; 65(1):57-64. DOI: 10.1152/jappl.1988.65.1.57. View

19.

Duan W, Chan J, McKay K, Crosby J, Choo H, Leung B . Inhaled p38alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. Am J Respir Crit Care Med. 2004; 171(6):571-8. DOI: 10.1164/rccm.200408-1006OC. View

20.

Hakonarson H, Halapi E, Whelan R, Gulcher J, Stefansson K, Grunstein M . Association between IL-1beta/TNF-alpha-induced glucocorticoid-sensitive changes in multiple gene expression and altered responsiveness in airway smooth muscle. Am J Respir Cell Mol Biol. 2001; 25(6):761-71. DOI: 10.1165/ajrcmb.25.6.4628. View