Caveolin-2-deficient mice show increased sensitivity to endotoxemia

Cecilia J. De Almeida, Agnieszka K. Witkiewicz, Jean François Jasmin, Herbert B. Tanowitz, Federica Sotgia, Philippe G. Frank, Michael P. Lisanti

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Caveolin proteins are structural components of caveolae and are involved in the regulation of many biological processes. Recent studies have shown that caveolin-1 modulates inflammatory responses and is important for sepsis development. In the present study, we show that caveolin-1 and caveolin-2 have opposite roles in lipopolysaccharide (LPS)-induced sepsis using caveolin-deficient (Cav-1 -/- and Cav-2 -/-) mice for each of these proteins. While Cav-1 -/- mice displayed delayed mortality following challenge with LPS, Cav-2 -/- mice were more sensitive to LPS compared to wild-type (WT). With Cav-2 -/- mice, this effect was associated with increased intestinal injury and increased intestinal permeability. This negative outcome was also correlated with enhanced expression of iNOS in intestinal epithelial cells, and enhanced production of nitric oxide (NO). By contrast, Cav-1 -/- mice demonstrated a decrease in iNOS expression with decreased NO production, but no alteration in intestinal permeability. The differential expression of iNOS was associated with a significant increase in STAT-1 activation in these mice. Intestinal cells of Cav-2 -/- mice showed increased phosphorylation of STAT-1 at tyrosine 701 compared to wild-type. However, Cav-1 -/- mice-derived intestinal cells showed decreased levels of phosphorylation of STAT-1 at tyrosine 701. Since caveolin-2 is almost completely absent in Cav-1 -/- mice, we conclude that it is not just the absence of caveolin-2 that is responsible for the observed effects, but that the balance between caveolin-1 and caveolin-2 is important for iNOS expression and ultimately for sepsis outcome.

Original languageEnglish (US)
Pages (from-to)2151-2161
Number of pages11
JournalCell Cycle
Volume10
Issue number13
DOIs
StatePublished - Jul 1 2011

Fingerprint

Caveolin 2
Endotoxemia
Caveolin 1
Caveolins
Lipopolysaccharides
Sepsis
Tyrosine
Permeability
Nitric Oxide
Phosphorylation
Biological Phenomena
Caveolae
Epithelial Cells

Keywords

  • Caveolin
  • Endotoxemia
  • Inflammation
  • Lipopolysaccharide
  • Nitric oxide
  • Permeability
  • Sepsis

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

De Almeida, C. J., Witkiewicz, A. K., Jasmin, J. F., Tanowitz, H. B., Sotgia, F., Frank, P. G., & Lisanti, M. P. (2011). Caveolin-2-deficient mice show increased sensitivity to endotoxemia. Cell Cycle, 10(13), 2151-2161. https://doi.org/10.4161/cc.10.13.16234

Caveolin-2-deficient mice show increased sensitivity to endotoxemia. / De Almeida, Cecilia J.; Witkiewicz, Agnieszka K.; Jasmin, Jean François; Tanowitz, Herbert B.; Sotgia, Federica; Frank, Philippe G.; Lisanti, Michael P.

In: Cell Cycle, Vol. 10, No. 13, 01.07.2011, p. 2151-2161.

Research output: Contribution to journalArticle

De Almeida, CJ, Witkiewicz, AK, Jasmin, JF, Tanowitz, HB, Sotgia, F, Frank, PG & Lisanti, MP 2011, 'Caveolin-2-deficient mice show increased sensitivity to endotoxemia', Cell Cycle, vol. 10, no. 13, pp. 2151-2161. https://doi.org/10.4161/cc.10.13.16234
De Almeida CJ, Witkiewicz AK, Jasmin JF, Tanowitz HB, Sotgia F, Frank PG et al. Caveolin-2-deficient mice show increased sensitivity to endotoxemia. Cell Cycle. 2011 Jul 1;10(13):2151-2161. https://doi.org/10.4161/cc.10.13.16234
De Almeida, Cecilia J. ; Witkiewicz, Agnieszka K. ; Jasmin, Jean François ; Tanowitz, Herbert B. ; Sotgia, Federica ; Frank, Philippe G. ; Lisanti, Michael P. / Caveolin-2-deficient mice show increased sensitivity to endotoxemia. In: Cell Cycle. 2011 ; Vol. 10, No. 13. pp. 2151-2161.
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AB - Caveolin proteins are structural components of caveolae and are involved in the regulation of many biological processes. Recent studies have shown that caveolin-1 modulates inflammatory responses and is important for sepsis development. In the present study, we show that caveolin-1 and caveolin-2 have opposite roles in lipopolysaccharide (LPS)-induced sepsis using caveolin-deficient (Cav-1 -/- and Cav-2 -/-) mice for each of these proteins. While Cav-1 -/- mice displayed delayed mortality following challenge with LPS, Cav-2 -/- mice were more sensitive to LPS compared to wild-type (WT). With Cav-2 -/- mice, this effect was associated with increased intestinal injury and increased intestinal permeability. This negative outcome was also correlated with enhanced expression of iNOS in intestinal epithelial cells, and enhanced production of nitric oxide (NO). By contrast, Cav-1 -/- mice demonstrated a decrease in iNOS expression with decreased NO production, but no alteration in intestinal permeability. The differential expression of iNOS was associated with a significant increase in STAT-1 activation in these mice. Intestinal cells of Cav-2 -/- mice showed increased phosphorylation of STAT-1 at tyrosine 701 compared to wild-type. However, Cav-1 -/- mice-derived intestinal cells showed decreased levels of phosphorylation of STAT-1 at tyrosine 701. Since caveolin-2 is almost completely absent in Cav-1 -/- mice, we conclude that it is not just the absence of caveolin-2 that is responsible for the observed effects, but that the balance between caveolin-1 and caveolin-2 is important for iNOS expression and ultimately for sepsis outcome.

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