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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/L171    most recent 00457.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Moynihan, B. Articles by Martin, J. G. PubMed PubMed Citation Articles by Moynihan, B. Articles by Martin, J. G.

MAP kinases mediate interleukin-13 effects on calcium signaling in human airway smooth muscle cells

¹Meakins-Christie Laboratories, Department of Medicine, McGill University; and ²Notre Dame Hospital, Universite de Montreal, Montreal, Canada

Submitted 1 November 2007 ; accepted in final form 21 April 2008

Interleukin-13 (IL-13) has been strongly implicated in the pathogenesis of allergic asthma through animal models that have shown that IL-13 is both necessary and sufficient to cause airway hyperresponsiveness (AHR). Airway smooth muscle (ASM) is a primary effector of AHR, and IL-13 increases the responsiveness of ASM, by increasing Ca²⁺ release intracellularly, to bronchoconstrictors such as histamine. The mechanisms and signaling pathways mediating this effect are incompletely understood. We have investigated the pathways through which IL-13 regulates the Ca²⁺ response to histamine in primary human ASM cell cultures. Functional IL-13 receptors were demonstrated by IL-13-mediated phosphorylation of signal transducer and activator of transcription 6 (STAT6) and mitogen-activated protein kinases (MAPKs). IL-13 increased Ca²⁺ responses to histamine. The augmentation of Ca²⁺ signaling was not affected by inhibition of STAT6 or p38 MAPK signaling but was prevented by concurrent inhibition of c-jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) MAPKs. This inhibition did not affect the IL-13-induced increase in histamine receptors. We conclude that IL-13 induces potentiation of Ca²⁺ responses to contractile agonists by affecting mechanisms downstream of receptors. JNK and ERK MAPKs modulate these mechanisms.

lung; allergy; inflammation; cytokines; mitogen-activated protein kinase