Role of IL-8 and GRO-α in the chemotactic migration of all-trans retinoic acid treated promyelocytic leukemic cells toward alveolar epithelial cells

• Main Authors: Wen-Hui Tsai, 蔡玟蕙
• Other Authors: Yu Ru Kou
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/63621987782058376900

博士 === 國立陽明大學 === 生理學研究所 === 95 === Objective: Although all-trans retinoic acid ( ATRA) can treat acute promyelocytic leukemia (APL), it also causes retinoic acid (RA) syndrome with presentations similar to acute respiratory distress syndrome (ARDS). We investigated the role IL-8 and GRO-�� in the chemotactic transmigration of ATRA -treated NB4 (ATRA -NB4) APL cells toward A549 alveolar epithelial cells. Design: An in vitro human cell culture study. Setting: University hospital research laboratories Subjects and Interventions: NB4 and A549 cells were separately cultured with ATRA and/or dexsamethasone for 1-3 days. NB4 or ATRA -NB4 cells were then placed in an upper insert and co-incubated with A549 cells or their conditioned medium located in a lower plate. Measurements and Main Results: ATRA stimulated NB4 cells to transmigrate toward the A549 cells in a time- and dose-dependent manner. Replacement of A459 condition medium by its original medium abrogated this transmigration. Only A549 cells constitutively secreted GRO-�� and both A549 and NB4 cells constitutively secreted IL-8, which was enhanced by ATRA. Exogenous administration of IL-8 or GRO-�� also promoted the ATRA -NB4 transmigration. The binding assay demonstrated that ATRA -NB4 cells were more vulnerable to IL-8 binding than GRO-�� binding. Antibodies pretreatment against IL-8 and GRO-�� receptors reduced ATRA -NB4 transmigration by about 60%. Dexamethasone did not suppress their IL-8 secretion and transmigration in ATRA -NB4 cells, but when applied to A549 cells, IL-8 secretion was suppressed but not GRO-�� secretion, and there was attenuation of ATRA -NB4 transmigration. Conclusions: We concluded that IL-8 and GRO-�� secreted from alveolar epithelial cells play an important role in the cell-cell interaction involved in the chemotactic transmigration of ATRA -treated APL cells toward alveolar epithelial cells.