期刊
JOURNAL OF IMMUNOLOGY
卷 164, 期 12, 页码 6322-6331出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.164.12.6322
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- NHLBI NIH HHS [HL30568, HL57008] Funding Source: Medline
A new murine chemokine was identified in a search for glucocorticoid-attenuated response genes induced in the lung during endotoxemia. The first 73 residues of the predicted mature peptide are 71% identical and 93% similar to human CXCL11/IFN-inducible T cell alpha chemoattractant (I-TAC) (alias beta-R1, H174, IFN-inducible protein 9 (IP-9), and SCYB9B), The murine chemokine has six additional residues at the carboxyl terminus not present in human I-TAG. Identification of this cDNA as murine CXCL11/I-TAC is supported by phylogenetic analysis and by radiation hybrid mapping of murine I-TAG (gene symbol Scyb11) to mouse chromosome 5 close to the genes for monokine induced by IFN-gamma (MIG) and IP10, Murine I-TAG mRNA is induced in RAW 264.7 macrophages by IFN-gamma or LPS and is weakly induced by IFN-alpha beta. IFN-gamma induction of murine I-TAG Is markedly enhanced by costimulation with LPS or IL-1 beta in RAW cells and by TNF-cu in both RAW cells and Swiss 3T3 fibroblasts. Murine I-TAG is induced in multiple tissues during endoxemia, with strongest expression in lung, heart, small intestine, and kidney, a pattern of tissue expression different from those of MIG and IP10, Peak expression of I-TAG message is delayed compared with IP10, both in lung after i.v. LPS and in RAW 264.7 cells treated with LPS or with IFN-gamma. Pretreatment with dexamethasone strongly attenuates both IFN-gamma-induced I-TAG expression in RAW cells and endotoxemia-induced I-TAG expression in lung and small intestine. The structural and regulatory similarities of murine and human I-TAG suggest that mouse models will be useful for investigating the role of this chemokine in human biology and disease.
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