| First Author | Chandrasekar B | Year | 2013 |
| Journal | J Infect Dis | Volume | 207 |
| Issue | 10 | Pages | 1556-68 |
| PubMed ID | 23431040 | Mgi Jnum | J:315268 |
| Mgi Id | MGI:6829951 | Doi | 10.1093/infdis/jit067 |
| Citation | Chandrasekar B, et al. (2013) Regulation of chemokines, CCL3 and CCL4, by interferon gamma and nitric oxide synthase 2 in mouse macrophages and during Salmonella enterica serovar typhimurium infection. J Infect Dis 207(10):1556-68 |
| abstractText | BACKGROUND: Interferon gamma (IFN-gamma) increases the expression of multiple genes and responses; however, the mechanisms by which IFN-gamma downmodulates cellular responses is not well understood. In this study, the repression of CCL3 and CCL4 by IFN-gamma and nitric oxide synthase 2 (NOS2) in macrophages and upon Salmonella typhimurium infection of mice was investigated. METHODS: Small molecule regulators and adherent peritoneal exudates cells (A-PECs) from Nos2(-/-)mice were used to identify the contribution of signaling molecules during IFN-gamma-mediated in vitro regulation of CCL3, CCL4, and CXCL10. In addition, infection of bone marrow-derived macrophages (BMDMs) and mice (C57BL/6, Ifn-gamma(-/), and Nos2(-/-)) with S. typhimurium were used to gain an understanding of the in vivo regulation of these chemokines. RESULTS: IFN-gamma repressed CCL3 and CCL4 in a signal transducer and activator of transcription 1 (STAT1)-NOS2-p38 mitogen activated protein kinase (p38MAPK)-activating transcription factor 3 (ATF3) dependent pathway in A-PECs. Also, during intracellular replication of S. typhimurium in BMDMs, IFN-gamma and NOS2 repressed CCL3 and CCL4 production. The physiological roles of these observations were revealed during oral infection of mice with S. typhimurium, wherein endogenous IFN-gamma and NOS2 enhanced serum amounts of tumor necrosis factor alpha and CXCL10 but repressed CCL3 and CCL4. CONCLUSIONS: This study sheds novel mechanistic insight on the regulation of CCL3 and CCL4 in mouse macrophages and during S. typhimurium oral infection. |
