Activation of epidermal growth factor receptor via CCR3 in bronchial epithelial cells.
We have previously found that bronchial epithelial cells express CCR3 whose signaling elicits mitogen-activated protein (MAP) kinase activation and cytokine production. Several investigators have focused on the signaling crosstalk between G protein-coupled receptors (GPCRs) and epidermal growth factor receptor (EGFR) in cancer cells. In this study, we investigated the role of EGFR in CCR3 signaling in the bronchial epithelial cell line NCI-H292. Eotaxin (1-100 nM) induced dose-dependent tyrosine phosphorylation of EGFR in NCI-H292 cells. Pretreatment of the cells with the EGFR inhibitor (AG1478) significantly inhibited the MAP kinase phosphorylation induced by eotaxin. Eotaxin stimulated IL-8 production, which was inhibited by AG1478. The transactivation of EGFR through CCR3 is a critical pathway that elicits MAP kinase activation and cytokine production in bronchial epithelial cells. The delineation of the signaling pathway of chemokines will help to develop a new therapeutic strategy to allergic diseases including bronchial asthma.
Adachi
Tetsuya
T
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. tadachi@med.teikyo-u.ac.jp
Cui
Chang-Hao
CH
Kanda
Akira
A
Kayaba
Hiroyuki
H
Ohta
Ken
K
Chihara
Junichi
J
D001980:Bronchi / Q000166:cytology / Q000502:physiology*; D002460:Cell Line; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D010766:Phosphorylation; D011799:Quinazolines; D020239:Receptor Cross-Talk; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016209:Interleukin-8; D011799:Quinazolines; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D020032:Tyrphostins; C101044:RTKI cpd; D014443:Tyrosine; D066246:ErbB Receptors