TY - JOUR
T1 - Lysophosphatidic acid induces interleukin-13 (IL-13) receptor α2 expression and inhibits IL-13 signaling in primary human bronchial epithelial cells
AU - Zhao, Yutong
AU - He, Donghong
AU - Zhao, Jing
AU - Wang, Lixin
AU - Leff, Alan R.
AU - Spannhake, Ernst Wm
AU - Georas, Steve
AU - Natarajan, Viswanathan
PY - 2007/4/6
Y1 - 2007/4/6
N2 - Interleukin-13 (IL-13), a Th2 cytokine, plays a pivotal role in pathogenesis of bronchial asthma via IL-13 receptor α1 (IL-13Rα1) and IL-4 receptor α(IL-4Rα). Recent studies show that a decoy receptor for IL-13, namely IL-13Rα2, mitigates IL-13 signaling and function. This study provides evidence for regulation of IL-13Rα2 production and release and IL-13-dependent signaling by lysophosphatidic acid (LPA) in primary cultures of human bronchial epithelial cells (HBEpCs). LPA treatment of HBEpCs in a time-dependent fashion increased IL-13Rα2 gene expression without altering the mRNA levels of IL-13Rα1 and IL-4Rα. Pretreatment with pertussis toxin (100 ng/ml, 4 h) or transfection of c-Jun small interference RNA or an inhibitor of JNK attenuated LPA-induced IL-13Rα2 gene expression and secretion of soluble IL-13Rα2. Overexpression of catalytically inactive mutants of phospholipase D(PLD) 1 or 2 attenuated LPA-induced IL-13Rα2 gene expression and protein secretion as well as phosphorylation of JNK. Pretreatment of HBEpCs with 1 μM LPA for 6 h attenuated IL-13- but not IL-4-induced phosphorylation of STAT6. Transfection of HBEpCs with IL-13Rα2 small interference RNA blocked the effect of LPA on IL-13-induced phosphorylation of STAT6. Furthermore, pretreatment with LPA (1 μM, 6 h) attenuated IL-13-induced eotaxin-1 and SOCS-1 gene expression. These results demonstrate that LPA induces IL-13Rα2 expression and release via PLD and JNK/AP-1 signal transduction and that pretreatment with LPA down-regulates IL-13 signaling in HBEpCs. Our data suggest a novel mechanism of regulation of IL-13Rα2 and IL-13 signaling that may be of physiological relevance to airway inflammation and remodeling.
AB - Interleukin-13 (IL-13), a Th2 cytokine, plays a pivotal role in pathogenesis of bronchial asthma via IL-13 receptor α1 (IL-13Rα1) and IL-4 receptor α(IL-4Rα). Recent studies show that a decoy receptor for IL-13, namely IL-13Rα2, mitigates IL-13 signaling and function. This study provides evidence for regulation of IL-13Rα2 production and release and IL-13-dependent signaling by lysophosphatidic acid (LPA) in primary cultures of human bronchial epithelial cells (HBEpCs). LPA treatment of HBEpCs in a time-dependent fashion increased IL-13Rα2 gene expression without altering the mRNA levels of IL-13Rα1 and IL-4Rα. Pretreatment with pertussis toxin (100 ng/ml, 4 h) or transfection of c-Jun small interference RNA or an inhibitor of JNK attenuated LPA-induced IL-13Rα2 gene expression and secretion of soluble IL-13Rα2. Overexpression of catalytically inactive mutants of phospholipase D(PLD) 1 or 2 attenuated LPA-induced IL-13Rα2 gene expression and protein secretion as well as phosphorylation of JNK. Pretreatment of HBEpCs with 1 μM LPA for 6 h attenuated IL-13- but not IL-4-induced phosphorylation of STAT6. Transfection of HBEpCs with IL-13Rα2 small interference RNA blocked the effect of LPA on IL-13-induced phosphorylation of STAT6. Furthermore, pretreatment with LPA (1 μM, 6 h) attenuated IL-13-induced eotaxin-1 and SOCS-1 gene expression. These results demonstrate that LPA induces IL-13Rα2 expression and release via PLD and JNK/AP-1 signal transduction and that pretreatment with LPA down-regulates IL-13 signaling in HBEpCs. Our data suggest a novel mechanism of regulation of IL-13Rα2 and IL-13 signaling that may be of physiological relevance to airway inflammation and remodeling.
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U2 - 10.1074/jbc.M611210200
DO - 10.1074/jbc.M611210200
M3 - Article
C2 - 17287216
AN - SCOPUS:34249862134
SN - 0021-9258
VL - 282
SP - 10172
EP - 10179
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 14
ER -