https://scholars.lib.ntu.edu.tw/handle/123456789/593968
標題: | EGF receptor-dependent mechanism may be involved in the Tamm-Horsfall glycoprotein-enhanced PMN phagocytosis via activating Rho family and MAPK signaling pathway | 作者: | KO-JEN LI Siao, Sue-Cien CHENG-HAN WU CHIEH-YU SHEN Wu, Tsai-Hung Tsai, Chang-Youh SONG-CHOU HSIEH CHIA-LI YU |
關鍵字: | Tamm-Horsfall glycoprotein; phagocytosis; EGF-like domains; Rho family; MAP kinase; JUVENILE HYPERURICAEMIC NEPHROPATHY; FACTOR-LIKE DOMAIN; MEDIATED PHAGOCYTOSIS; URINARY GLYCOPROTEIN; HUMAN NEUTROPHILS; PROTEIN BINDS; UROMODULIN; CDC42; GLYCOSYLATION; EXPRESSION | 公開日期: | 21-一月-2014 | 出版社: | MDPI AG | 卷: | 19 | 期: | 1 | 起(迄)頁: | 1328 | 來源出版物: | Molecules (Basel, Switzerland) | 摘要: | Our previous studies showed that urinary Tamm-Horsfall glycoprotein (THP) potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the domain structure(s), signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human promyelocytic leukemia cell line HL-60 was induced to differentiate into PMNs by all-trans retinoid acid. Pretreatment with different MAPK and PI3K inhibitors was used to delineate signaling pathways in THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN phagocytosis induced by bacterial lipopolysaccharide (LPS), THP, or human recombinant epidermal growth factor (EGF) was evaluated by western blot. A p38 MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP-induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974 significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by activating Rho family and MAP kinase. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/593968 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules19011328 |
顯示於: | 醫學系 |
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