Key result
Lipopolysaccharide stimulation up-regulated caveolin-1 expression in normal murine peritoneal macrophages at 1.0 pg/ml, but required 10,000-fold higher doses in hyporesponsive cells.
Caveolin-1 expression is differentially regulated by LPS in various murine macrophage models, suggesting a potential role in LPS signaling and internalization.
Hypothesis-generating in murine models; leaves open caveolin-1's role in human LPS signaling pending validation.
Five reciprocal cycles of subtractive hybridization using cDNA generated from fibroblasts with normal lipopolysaccharide (LPS) responsiveness (lps(n)) and from hyporesponsive (lps(d)) fibroblasts have led to the finding that caveolin-1 is expressed at markedly higher levels of mRNA in lps(d) than in lps(n) fibroblasts. Caveolin-1 message can also be readily detected via reverse transcription-PCR in the RAW264.7 and J774.1 macrophage-like cell lines as well as in primary thioglycolate (TG)-elicited mouse peritoneal macrophages. In RAW264.7 cells, both caveolin-1 mRNA and protein levels are down-regulated by LPS. In TG-elicited C3HeB/FeJ peritoneal macrophages, in contrast, expression of both caveolin-1 protein and mRNA is up-regulated in vitro in response to LPS stimulation. The up-regulation of caveolin-1 protein expression in C3HeB/FeJ peritoneal macrophages can be demonstrated at concentrations as low as 1.0 pg of LPS/ml. However, LPS concentrations approximately 4 orders of magnitude higher (10(4) pg/ml) were required to stimulate the LPS-hyporesponsive C3H/HeJ mice peritoneal macrophages such that significant caveolin-1 protein up-regulation was detected. Caveolin-1, a principal component of plasmalemmal caveolae, has been reported as a potentially important regulator for signal transduction during cellular stimulation. The results described in this report suggest that caveolin-1 expression may be associated with LPS signaling/internalization.
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Lei et al. (2000) studied LPS responsiveness. Lipopolysaccharide (LPS) vs. Unstimulated cells / LPS-hyporesponsive cells was evaluated on Caveolin-1 mRNA and protein expression. Lipopolysaccharide stimulation up-regulated caveolin-1 expression in normal murine peritoneal macrophages at 1.0 pg/ml, but required 10,000-fold higher doses in hyporesponsive cells.
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