Role of Caveolin Proteins in Sepsis

Abstract

Despite the progress in medical treatment sepsis remains one of the major causes of death in pediatric and elderly patients. Understanding signaling pathways associated with sepsis may be of key significance for designing more efficient therapeutic approaches which could alleviate sepsis outcome. Earlier studies suggested that cholesteroland sphingolipid-rich lipid rafts and their morphologically distinct subset, caveolaecan be utilized by certain bacterial pathogens to enter and invade host cells. Moreover, there is also evidence that the expression levels of the major caveolar coat proteincaveolin-1 can be regulated by the major component of the outer membrane of Gram-negative bacteria,lipopolysaccharide (LPS) in various cell types involved in sepsis. In particular recent studies using caveolin-1 knockout mice and cells have revealed that caveolin-1 is directly involved in regulating numerous signalingpathways and functions in various cell types of the immune system and other cell types involved in sepsis. Moreover, the most recent report implies that in addition to extensively studied caveolin-1, caveolin-2 is also important in regulating LPS-induced sepsis and might possibly play an opposite role to caveolin-1 in regulating certain pro-inflammatory signaling pathways. The purpose of this review is to discuss these new exciting discoveries relatedto the specific role of caveolin-1 and the less studiedcaveolin-2in regulating signaling and outcome associated with sepsis induced by LPS and pathogenic bacteria at molecular, cellular and systemic levels.