title: Sodium azide suppresses LPS-induced expression MCP-1 through regulating IκBζ and STAT1 activities in macrophages.
abstract: Sodium azide (NaN3) is a chemical compound with multiple toxic effects on vascular and neuronal systems, causing hypotension and neurotoxicity, respectively. In order to test its effects on the immune system, human and mouse macrophage-like cell lines were treated with nontoxic doses of NaN3and the changes in LPS-induced inflammatory activation was measured. Interestingly, the LPS-induced expression of monocyte chemoattractant protein (MCP)-1 was suppressed by NaN3without affecting the expression of IL-8 and TNF-α. Further analysis of cellular signaling mediators involved in the expression of these cytokines revealed that NaN3suppressed the LPS-induced activation of signal transducers and activator of transcription (STAT)1 and inhibitor of κB (IκB) ς, which are involved in the LPS-induced expression of MCP-1, while the LPS-induced activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) was not affected. The LPS-induced expression of MCP-2 and CXCL10, which are also regulated by STAT1, was suppressed by NaN3. Similarly, the LPS-induced expression of IL-6, which is regulated by IκBζ, was suppressed by NaN3. These results demonstrate that NaN3selectively suppresses the LPS-induced expression of pro-inflammatory mediators through the suppression of STAT1 and IκBζ activation. These new findings about the activity of NaN3may contribute to the development of specific regulators of macrophage activity during acute and chronic inflammation.
authors.affiliation: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Cho-Yi
authors.initials: CY
authors.lastname: Park
authors.affiliation: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Jae-Nyoung
authors.initials: JN
authors.lastname: Heo
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.affiliation: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: whl@knu.ac.kr.
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors; D000818:Animals; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D000067996:RAW 264.7 Cells; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019810:Sodium Azide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C111835:CCL2 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C417234:NFKBIZ protein, human; C485947:Nfkbiz protein, mouse; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019810:Sodium Azide
keywords: IκBζ; LPS; MCP-1; Macrophage; STAT1; Signaling