Lipopolysaccharide-induced p38α signaling in the regulation of macrophage phagocytosing E. coli

• Main Authors: Wei-Ting Wang, 王薇婷
• Other Authors: Hsien-Yeh Hsu
• Format: Others
• Language: en_US
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/16976711496643553983

碩士 === 國立陽明大學 === 醫學生物技術研究所 === 93 === Our previous results demonstrated that LPS-induced pro-inflammatory cytokine proIL-1 production is p38 phosphorylation-dependent from murine macrophage J774A.1 cells. In addition, LPS stimulates cells to produce ROS within 15 min (Hsu, H. Y., and Wen, M. H. (2002) J. Biol.Chem. 277, 22131–22139). Our data reported that there is only one member of p38MAPK family, p38α, in J774A.1 cells. To examine further the role of p38α in LPS-induced signal transduction in the regulation of phagocytosis of E. coli-FITC, we utilized p38α dominant-negative plasmid (DN-p38α) transfected J774A.1 and SB203580, a pharmacological antagonist of p38. We demonstrated that LPS-induced NADPH oxidase activity and ROS within 30 min, which involved p38α phosphorylation. Interestingly, p38α phosphorylation is needed to regulate one of key component of NADPH oxidase; Rac activity; but p38α activation does not regulate the translocation of cytosolic protein; p47phox, p67 phox. On the other hand, p38α phosphorylation participates in protein expression of macrophage scavenger receptor (MSR), internalization of E.coli-FITC, phagolysosome fusion and the ability of macrophages phagocytosing E. coli-FITC. Our results indicate that LPS-induced p38α phosphorylation involve NADPH oxidase assembly and accelerate phagocytosis ability. Our current findings should provide a model that LPS, the component of gram-negative bacteria, induces the signaling of phagocytosis, improves the expression of MSR, enhances the ability of phagocytosis, and promotes phagosome and lysosome fusion is p38α activation dependent in murine macrophage-like J774A.1 cells.