Studies of Bacterial Lipoproteins-Mediated Signal Transduction and Cytokine Induction in Macrophage

• Main Authors: Shih-Chi Su, 蘇仕奇
• Other Authors: Hsien-Yeh Hsu
• Format: Others
• Language: en_US
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/46710396472429791915

碩士 === 國立陽明大學 === 醫學生物技術研究所 === 89 === Abstract Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are the major component of cell walls of Gram-positive and Gram-negative bacteria respectively, also the inducers of septic syndrome. In this study, we have examined the ability of LTA and LPS to trigger the activation of intrinsic signal pathways as well as to induce the release of tumor necrosis factor  (TNF) and interleukin-1(IL-1) in murine macrophage J774A.1. Our results indicated that the signaling pathways triggered by LTA or LPS are approximately similar. We investigated that the Src family protein tyrosine kinases (PTK), Src and Lyn, and three MAP kinases (Erk, p38, and JNK) are involved in both LTA and LPS signaling. By using various protein kinase inhibitors prior to cell stimulation, we further identified the role of several signaling events, including PKC, PI-3-kinase, Erk, JNK and p38 in regulations of TNF and IL-1induction during response to LTA or LPS. Our data presented in this study suggest that LTA and LPS trigger inflammatory cytokines through similar intracellular pathway, and which is PI-3-kinase dependent and PKC independent. However, TNFand IL-1 induction are differentially mediated by distinct MAP kinases. Respectively, Erk1/Erk2 pathway is critically involved in TNFinduction but not responsible for IL-1 induction. The p38 MAP kinase plays a pivotal role in regulation of IL-1 biosynthesis but moderately controls the release of TNF. Relatively, the role of JNK is minor, and solely modulates the translation in both cases.