title: Interleukin-13 enhanced Ca2+ oscillations in airway smooth muscle cells.
abstract: 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 50 μM 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.
authors.affiliation: Department of Respiratory Medicine, Kyoto University, Kyoto, Japan. hmatsumo@kuhp.kyoto-u.ac.jp
authors.forename: Hisako
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirata
authors.forename: Kojiro
authors.initials: K
authors.lastname: Otsuka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Iwata
authors.forename: Aya
authors.initials: A
authors.lastname: Inazumi
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.forename: Emiko
authors.initials: E
authors.lastname: Ogawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Muro
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chin
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Oku
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism; D000368:Aged; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology; D008168:Lung / Q000473:pathology*; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000235:genetics / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D001896:Boron Compounds; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018793:Interleukin-13; D047028:Macrocyclic Compounds; D010080:Oxazoles; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D019837:Ryanodine Receptor Calcium Release Channel; D050052:TRPC Cation Channels; C511704:xestospongin C; D012430:Ruthenium Red; D012433:Ryanodine; D017998:Leukotriene D4; C109986:2-aminoethoxydiphenyl borate; D051997:ADP-ribosyl Cyclase 1; C083169:leukotriene D4 receptor; D002118:Calcium