EXPRESSION OF THE CONNEXIN-43 GENE IS INCREASED IN THE KIDNEYS AND THE LUNGS OF RATS INJECTED WITH BACTERIAL LIPOPOLYSACCHARIDE

At the molecular level, the inflammatory response is characterized by changes in gene expression of various organ systems. One gene by which expression has been observed to be altered in the liver during inflam mation is connexin (Gx) 32. Ox genes encode the polypeptide subunits o f the hemichannels that comprise gap junctions. In the present study, an increase in the expression of a different Cx gene, Cx43, was observ ed in the kidney and lung of rats injected with a sublethal dose (1 mg /kg) of bacterial lipolysaccharide (LPS). To elucidate the possible me chanism by which the Cx43 expression is increased during inflammation, the 5' flanking region of the gene was cloned and coupled to a report er gene (human growth hormone). This construct was transfected into ce lls of renal origin (NRK), which express Cx43 constitutively. The Cx43 promoter activity was indeed found in the cloned region, which contai ned 725 base pairs upstream of the transcriptional initiation site of the Cx43 gene. The Cx43 promoter activity was found to be increased by incubation of the transfected cells with serum obtained from LPS-trea ted rats. Moreover, direct incubation of the transfected cells with LP S or interleukin 1 beta, but not with other cytokines, was observed to increase the Cx43 promoter activity. These results suggest the expres sion of Cx43 after administration of LPS is part of the inflammatory r esponse. Moreover, the expression of this gene seems to be mediated by proinflammatory mediators.