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 inflammation is connexin (Cx) 32. Cx genes encode the polypeptide subunits of the hemichannels that comprise gap junctions. In the present study, an increase in the expression of a different Cx gene, Cx43, was observed in the kidney and lung of rats injected with a sublethal dose (1 mg/kg) of bacterial lipolysaccharide (LPS). To elucidate the possible mechanism by which the Cx43 expression is increased during inflammation, the 5' flanking region of the gene was cloned and coupled to a reporter gene (human growth hormone). This construct was transfected into cells of renal origin (NRK), which express Cx43 constitutively. The Cx43 promoter activity was indeed found in the cloned region, which contained 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-treated rats. Moreover, direct incubation of the transfected cells with LPS or interleukin 1beta, but not with other cytokines, was observed to increase the Cx43 promoter activity. These results suggest the expression of Cx43 after administration of LPS is part of the inflammatory response. Moreover, the expression of this gene seems to be mediated by proinflammatory mediators.
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
M
M
Fernandez-Cobo
C
C
Gingalewski
A
A
De Maio
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics*; D004926:Escherichia coli; D017629:Gap Junctions / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007668:Kidney; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018031:Connexin 43; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma