Impaired Cd14 and Cd36 expression, bacterial clearance, and Toll-like receptor 4-Myd88 signaling in caveolin-1-deleted macrophages and mice

• Published in: Shock (Augusta, Ga.) Ga.), 2011-01, Vol.35 (1), p.92-99
• Main Authors: Tsai, Tsung-Huang, Chen, Shu-Fen, Huang, Tai-Yu, Tzeng, Chun-Fu, Chiang, Ann-Shyn, Kou, Yu Ru, Lee, Tzong-Shyuan, Shyue, Song-Kun
• Format: Article
• Language: English
• Subjects: Animals; Caveolin 1 - genetics; CD36 Antigens - metabolism; Cell Line; Cells, Cultured; Escherichia coli - immunology; Flow Cytometry; Immunoblotting; Lipopolysaccharide Receptors - metabolism; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Mice; Mice, Inbred C57BL; Myeloid Differentiation Factor 88 - metabolism; Phagocytosis - genetics; Phagocytosis - immunology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - physiology; Toll-Like Receptor 4 - metabolism
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0b013e3181ea45ca

An overwhelming immune response, particularly from macrophages, with gram-negative bacteria-induced sepsis plays a critical role in survival of and organ damage in infected patients. Caveolin-1 (Cav-1), a major structure protein of caveolae, regulates many cellular functions. We examined the vital role of Cav-1 in the response of macrophages and mice to bacteria or LPS exposure. Deletion of Cav-1 decreased the expression of CD14 and CD36 during macrophage differentiation and suppressed their phagocytotic ability. As well, the ability to kill bacteria was inhibited in Cav-1 macrophages and mice peritoneal cavity, tissue, and plasma, which was partly attributed to hindered expression of iNOS induced by bacteria or LPS. Furthermore, deletion of Cav-1 attenuated the expression of Toll-like receptor 4 and myeloid differentiation factor 88 and the activation of nuclear factor κB, all of which impeded the production of inflammatory cytokines in response to bacterial exposure in Cav-1 macrophages and mice. Thus, Cav-1 participates in the regulation of CD14, CD36, Toll-like receptor 4 and myeloid differentiation factor 88 protein expression and is crucial for the immune response of macrophages to bacterial infection. Cav-1 may be a therapeutic target in the treatment of sepsis.