Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial epithelial cells *

22 Concerted Expression of Eotaxin-1, Eotaxin-2, and Eotaxin-3 in Human Bronchial Epithelial Cells A. Komiya], H. Nagase l, H. Yamada 2, T. Sekiya t, M. Yamaguchi l, Y. Sano 2, N. Hanai 3, A. Fumya 3, K. Ohta 4, O. Yoshie 5, K. Yamamoto I, K. Hirail; 1Univ. of Tokyo Graduate School of Medicine, Tokyo, JAPAN, 2Doai Memorial Hospital, Tokyo, JAPAN, 3Kyowa Hakko Kogyo, Tokyo, JAPAN, 4Teikyo University School of Medicine, Tokyo, JAPAN, 5Kinki University School of Medicine, Osaka, JAPAN. CC chemokine receptor (CCR) 3 plays a pivotal role in peribronchial accumulation of eosinophils in allergic airway diseases. Eotaxin1/CCLI 1, eotaxin-2/CCL24 and eotaxin-3/CCL26 bind specifically and exclusively to CCR3. When bronchial biopsy specimens were analyzed for the protein expression of these chemokines, we observed increased expression of both eotaxin-2 and eotaxin-3 in addition to eotaxin-1 in the bronchial epithelium of asthmatics. We have investigated the production of eotaxin-l , -2 and -3 in various types of cells including bronchial epithelial cells. Protein production was measured by ELISA, and the levels of mRNA were analyzed by real-time PCR. EotaxinI, -2 and -3 was most potently secreted by fibroblasts (-60 ng/ml), monocytes (~50 ng/ml) and vascular endothelial cells (~1 mg/ml), respectively. Eotaxin-1 was also generated by BEAS-2B cells (-15 ng/ml). Eotaxin-2 was also secreted by A549 cells (~5 ng/ml) and to a lesser extent by normal human bronchial epithelial cells (NHBEC) (~100 pg/ml). In addition, A549 cells (~50 ng/ml), BEAS-2B cells (~30 ng/ml) and NHBEC (-5 ng/ml) all secreted considerable amount of eotaxin-3. As in the case of the production of eotaxin-l, generation of eotaxin-2 and eotaxin-3 by bronchial epithelial cells was up-regulated by IL-4 and IL-13, and attenuated by IFN-gamma and glucocorticoids. Expression of both eotaxin-2 and eotaxin-3 showed rather prolonged kinetics. These findings suggest that not just only eotaxin-I expression, hut also eotaxin-2 and eotaxin-3 expression in the bronchial epithelium might be able to be used in the therapeutic strategy for eosinophilic airway diseases. Funding: Grant Monies 23 Demonstration of Interleukin-9 Receptor Function in Human Germinal Center B Cells