Impaired Cd14 and Cd36 expression, bacterial clearance, and Toll-like receptor 4-Myd88 signaling in caveolin-1-deleted macrophages and mice.
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.
Tsai
Tsung-Huang
TH
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Chen
Shu-Fen
SF
Huang
Tai-Yu
TY
Tzeng
Chun-Fu
CF
Chiang
Ann-Shyn
AS
Kou
Yu Ru
YR
Lee
Tzong-Shyuan
TS
Shyue
Song-Kun
SK
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology; D005434:Flow Cytometry; D015151:Immunoblotting; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D018955:CD36 Antigens; D051242:Caveolin 1; D018950:Lipopolysaccharide Receptors; D053594:Myeloid Differentiation Factor 88; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4