Interleukin-13 enhanced Ca[2+] oscillations in airway smooth muscle cells.
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Physiological mechanisms associated with interleukin-13 (IL-13), a key cytokine in asthma, in intracellular Ca[2+] signaling in airway smooth muscle cells (ASMCs) remain unclear. The aim of this study was to assess effects of IL-13 on Ca[2+] oscillations in response to leukotriene D4 (LTD4) in human cultured ASMCs. LTD4-induced Ca[2+] oscillations in ASMCs pretreated with IL-13 were imaged by confocal microscopy. mRNA expressions of cysteinyl leukotriene 1 receptors (CysLT1R), CD38, involved with the ryanodine receptors (RyR) system, and transient receptor potential canonical (TRPC), involved with store-operated Ca[2+] entry (SOCE), were determined by real-time PCR. In IL-13-pretreated ASMCs, frequency of LTD4-induced Ca[2+] oscillations and number of oscillating cells were significantly increased compared with untreated ASMCs. Both xestospongin C, a specific inhibitor of inositol 1,4,5-triphosphate receptors (IP[3]R), and ryanodine or ruthenium red, inhibitors of RyR, partially blocked LTD4-induced Ca[2+] oscillations. Ca[2+] oscillations were almost completely inhibited by 50μM of 2-aminoethoxydiphenyl borate (2-APB), which dominantly blocks SOCE but not IP[3]R at this concentration. Pretreatment with IL-13 increased the mRNA expressions of CysLT1R and CD38, but not of TRPC1 and TRPC3. We conclude that IL-13 enhances frequency of LTD4-induced Ca[2+] oscillations in human ASMCs, which may be cooperatively modulated by IP[3]R, RyR systems and possibly by SOCE.
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