Regulation of cellular caveolin-1 protein expression in murine macrophages by microbial products.
Previously, we reported that expression of caveolin-1 in elicited peritoneal mouse macrophages was up-regulated by remarkably low (1.0-pg/ml) concentrations of Escherichia coli O111 lipopolysaccharide (LPS). Here we report that increases in caveolin-1 expression are manifested by different types of LPS, LPS-mimetic taxol, and heat-killed E. coli and to a much lesser extent by zymosan, polysaccharide-peptidoglycan, and heat-killed Staphylococcus aureus. Rhodobacter sphaeroides lipid A (RsDPLA) could not induce caveolin-1 expression in macrophages. Interestingly, polymyxin B (5 microg/ml) and RsDPLA show only a limited capacity to inhibit LPS-induced caveolin-1 expression. These findings suggest that expression of caveolin-1 in response to LPS may only partially be dependent upon lipid A. Recombinant tumor necrosis factor alpha marginally induces caveolin-1, suggesting that the ability of LPS to regulate caveolin-1 is not mediated primarily through an autocrine/paracrine mechanism involving this cytokine. Under conditions in which cellular levels of caveolin-1 are profoundly induced, no significant changes in TLR4 expression are observed. Of interest, caveolin-1 appears to localize to two cellular compartments, one associated with lipid rafts and a second associated with TLR4. Gamma interferon treatment inhibits the induction of caveolin-1 by LPS in macrophages. Inhibition of the p38 kinase-dependent pathway, but not the extracellular signal-regulated kinase pathway, effectively reduced the ability of LPS to mediate caveolin-1 up-regulation. Lactacystin, a potent inhibitor of the proteasome pathway, significantly modulates LPS-independent caveolin-1 expression, and lactacystin inhibits LPS-triggered caveolin-1 responses. These studies suggest that caveolin-1 up-regulation in response to LPS is likely to be proteasome dependent and triggered through the p38 kinase pathway.
Lei
Mei G
MG
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Slot 511, 4301 W. Markham St., Little Rock, AR 72205, USA. mglei@uams.edu
Tan
Xiaoyu
X
Qureshi
Nilofer
N
Morrison
David C
DC
D000818:Animals; D051242:Caveolin 1 / Q000032:analysis / Q000378:metabolism*; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D061988:Proteasome Inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D012242:Rhodobacter sphaeroides / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D051242:Caveolin 1; D008070:Lipopolysaccharides; D061988:Proteasome Inhibitors; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases