Differential regulation of gap junctions by proinflammatory mediators in vitro.

The development of inflammation is an important component of host defense against infection. The cellular and molecular processes underlying inflammation are well-studied, and it is known that cells of the blood vessel wall, such as endothelial cells and smooth muscle cells, play pivotal roles. Additionally, a wide variety of proinflammatory mediators have been defined, which coordinate the multicellular processes of inflammation. Knowledge of the potential role of blood vessel gap junctional intercellular communication (GJIC) in coordinating the inflammation process, however, is limited. In this study, we report that bacterial lipopolysaccharide (LPS), as well as the proinflammatory cytokines TNF-alpha and IL-1beta, selectively inhibit human myoendothelial GJIC in vitro without affecting GJIC between the respective homologous cell populations. This finding may represent a physiologically relevant component of the inflammatory response to infection. The work also provides some of the first clear evidence suggesting that a single eukaryotic cell can differentially regulate its GJIC between homologous and heterologous cell types in a simultaneous manner.