Cross-talk between calcineurin and protein kinases in airway remodeling in asthma / 北京大学学报(医学版)

ABSTRACT

Objective: To determine the role of cross-talk between calcineurin-dependent signal transduction pathway and protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) in airway remodeling in asthma. Methods: Male guinea pigs were sensitized with intraperitoneal injections of ovabumin (OVA), then treated with cyclosporin A (CsA,5 mg/kg), an inhibitor of calcineurin, then inhaled OVA for 2 weeks 14 days later. Activities of calcineurin, PKC, MAPK, and PKA were was analyzed by phosphorylation and dephosphorylation. In primary cultures of rat airway smooth muscle cells (ASMC), activities of calcineurin, PKC, MAPK, and cross-talk induced by urotensin Ⅱ (UⅡ), a recently identified strong mitogen, were measured. Results: (1) The activities of calcineurin, MAPK and PKC increased by 19% (P0.05). (4) CsA 10 -6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P0.05). Conclusion:The signal transduction pathways between calcineurin and other protein kinases such as PKC, MAPK and PKA have cross-talk in airway remodeling in asthma.