{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:31:30Z","timestamp":1789907490861,"version":"4.0.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Connexin 43 (Cx43) deficiency was found to increase mortality in a mouse model of bacterial peritonitis, and Cx43 is upregulated in macrophages by LPS treatment. In this study, we characterized a novel signaling pathway for LPS-induced Cx43 expression in RAW264.7 cells and thioglycolate-elicited peritoneal macrophages (TGEMs). LPS alone or LPS-containing conditioned medium (CM) upregulated Cx43. Overexpression or silencing of Cx43 led to the enhancement or inhibition, respectively, of CM-induced TGEM migration. This response involved the inducible NO synthase (iNOS)\/focal adhesion kinase (FAK)\/Src pathways. Moreover, CM-induced migration was compromised in TGEMs from Cx43+\/\u2212 mice compared with TGEMs from Cx43+\/+ littermates. Cx43 was upregulated by a serum\/glucocorticoid-regulated kinase 1 (SGK) activator and downregulated, along with inhibition of CM-induced TGEM migration, by knockdown of the SGK gene or blockade of the SGK pathway. LPS-induced SGK activation was abrogated by Torin2, whereas LPS-induced Cx43 was downregulated by both Torin2 and rapamycin. Analysis of the effects of FK506 and methylprednisolone, common immunosuppressive agents following organ transplantation, suggested a link between these immunosuppressive drugs and impaired macrophage migration via the Cx43\/iNOS\/Src\/FAK pathway. In a model of Escherichia coli infectious peritonitis, GSK650349-, an SGK inhibitor, or Torin2-treated mice showed less accumulation of F4\/80+CD11b+ macrophages in the peritoneal cavity, with a delay in the elimination of bacteria. Furthermore, following pretreatment with Gap19, a selective Cx43 hemichannel blocker, the survival of model mice was significantly reduced. Taken together, our study suggested that Cx43 in macrophages was associated with macrophage migration, an important immune process in host defense to infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1700954","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T15:15:42Z","timestamp":1539962142000},"page":"2986-2997","source":"Crossref","is-referenced-by-count":24,"title":["mTOR- and SGK-Mediated Connexin 43 Expression Participates in Lipopolysaccharide-Stimulated Macrophage Migration through the iNOS\/Src\/FAK Axis"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7026-3461","authenticated-orcid":false,"given":"Chen","family":"Shen","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University\u2013Biomedical Research Institute of Chonbuk National University Hospital , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0417-6236","authenticated-orcid":false,"given":"Jin Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University\u2013Biomedical Research Institute of Chonbuk National University Hospital , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngyi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chonbuk National University Medical School , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Mehedi","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Institute for Medical Science, Chonbuk National University Medical School , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University\u2013Biomedical Research Institute of Chonbuk National University Hospital , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Ulsan College of Medicine , Seoul 05505 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Tshool","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Institute for Medical Science, Chonbuk National University Medical School , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3768-4285","authenticated-orcid":false,"given":"Byung-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chonbuk National University Medical School , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University\u2013Biomedical Research Institute of Chonbuk National University Hospital , Jeonju 54907 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,15]]},"reference":[{"key":"2025030417574855500_r1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"Gordon","year":"2003","journal-title":"Nat. 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