Tags

Type your tag names separated by a space and hit enter

Importance of p38 mitogen-activated protein kinase pathway in allergic airway remodelling and bronchial hyperresponsiveness.
Eur J Pharmacol 2006; 544(1-3):160-7EJ

Abstract

p38 mitogen-activated protein kinase (MAPK) plays an important role in the activation of inflammatory cells and in the proliferation of airway structural cells. We investigated the role of p38 MAPK by using a selective inhibitor of p38 alpha and beta isoforms, SD282, in a chronic model of 15 ovalbumin exposures in sensitised mice using two doses (30 and 90 mg/kg). Allergen exposure induced bronchial hyperresponsiveness to methacholine as measured by the concentration of methacholine needed to increase pulmonary resistance by 200% (PC200), eosinophilia in bronchoalveolar lavage fluid and increase in airway smooth muscle area and goblet cell hyperplasia. In addition, p38 MAPK activity as measured by phosphorylated p38 expression on Western blots was increased after allergen challenge, which was suppressed by SD282 at both doses. SD282 inhibited bronchial hyperresponsiveness, but had no effect on eosinophils in bronchoalveolar lavage fluid. It also reduced airway smooth muscle and goblet cell hyperplasia, but had no effect on serum immunoglobulin E. p38 MAPK is involved in the pathogenesis of bronchial hyperresponsiveness but not in eosinophilic inflammation or the allergic response; however, remodelling features such as airway smooth muscle or goblet cell hyperplasia are regulated through p38 MAPK. Furthermore, bronchial hyperresponsiveness induced by chronic allergen exposure may be related to the development of airway wall remodelling.

Authors+Show Affiliations

National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16843456

Citation

Nath, Puneeta, et al. "Importance of P38 Mitogen-activated Protein Kinase Pathway in Allergic Airway Remodelling and Bronchial Hyperresponsiveness." European Journal of Pharmacology, vol. 544, no. 1-3, 2006, pp. 160-7.
Nath P, Leung SY, Williams A, et al. Importance of p38 mitogen-activated protein kinase pathway in allergic airway remodelling and bronchial hyperresponsiveness. Eur J Pharmacol. 2006;544(1-3):160-7.
Nath, P., Leung, S. Y., Williams, A., Noble, A., Chakravarty, S. D., Luedtke, G. R., ... Chung, K. F. (2006). Importance of p38 mitogen-activated protein kinase pathway in allergic airway remodelling and bronchial hyperresponsiveness. European Journal of Pharmacology, 544(1-3), pp. 160-7.
Nath P, et al. Importance of P38 Mitogen-activated Protein Kinase Pathway in Allergic Airway Remodelling and Bronchial Hyperresponsiveness. Eur J Pharmacol. 2006 Aug 21;544(1-3):160-7. PubMed PMID: 16843456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Importance of p38 mitogen-activated protein kinase pathway in allergic airway remodelling and bronchial hyperresponsiveness. AU - Nath,Puneeta, AU - Leung,Sum-Yee, AU - Williams,Alison, AU - Noble,Alistair, AU - Chakravarty,Sundeep Dugar Sarvajit, AU - Luedtke,Gregory R, AU - Medicherla,Satyanarayana, AU - Higgins,Linda S, AU - Protter,Andrew, AU - Chung,Kian Fan, Y1 - 2006/06/23/ PY - 2005/12/28/received PY - 2006/06/12/revised PY - 2006/06/15/accepted PY - 2006/7/18/pubmed PY - 2007/1/16/medline PY - 2006/7/18/entrez SP - 160 EP - 7 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 544 IS - 1-3 N2 - p38 mitogen-activated protein kinase (MAPK) plays an important role in the activation of inflammatory cells and in the proliferation of airway structural cells. We investigated the role of p38 MAPK by using a selective inhibitor of p38 alpha and beta isoforms, SD282, in a chronic model of 15 ovalbumin exposures in sensitised mice using two doses (30 and 90 mg/kg). Allergen exposure induced bronchial hyperresponsiveness to methacholine as measured by the concentration of methacholine needed to increase pulmonary resistance by 200% (PC200), eosinophilia in bronchoalveolar lavage fluid and increase in airway smooth muscle area and goblet cell hyperplasia. In addition, p38 MAPK activity as measured by phosphorylated p38 expression on Western blots was increased after allergen challenge, which was suppressed by SD282 at both doses. SD282 inhibited bronchial hyperresponsiveness, but had no effect on eosinophils in bronchoalveolar lavage fluid. It also reduced airway smooth muscle and goblet cell hyperplasia, but had no effect on serum immunoglobulin E. p38 MAPK is involved in the pathogenesis of bronchial hyperresponsiveness but not in eosinophilic inflammation or the allergic response; however, remodelling features such as airway smooth muscle or goblet cell hyperplasia are regulated through p38 MAPK. Furthermore, bronchial hyperresponsiveness induced by chronic allergen exposure may be related to the development of airway wall remodelling. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16843456/Importance_of_p38_mitogen_activated_protein_kinase_pathway_in_allergic_airway_remodelling_and_bronchial_hyperresponsiveness_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00659-5 DB - PRIME DP - Unbound Medicine ER -