The murine chemokine CXCL11 (IFN-inducible T cell alpha chemoattractant) is an IFN-gamma- and lipopolysaccharide-inducible glucocorticoid-attenuated response gene expressed in lung and other tissues during endotoxemia.
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-TAC. Identification of this cDNA as murine CXCL11/I-TAC is supported by phylogenetic analysis and by radiation hybrid mapping of murine I-TAC (gene symbol Scyb11) to mouse chromosome 5 close to the genes for monokine induced by IFN-gamma (MIG) and IP10. Murine I-TAC mRNA is induced in RAW 264.7 macrophages by IFN-gamma or LPS and is weakly induced by IFN-alphabeta. IFN-gamma induction of murine I-TAC is markedly enhanced by costimulation with LPS or IL-1beta in RAW cells and by TNF-alpha in both RAW cells and Swiss 3T3 fibroblasts. Murine I-TAC 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-TAC 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-TAC expression in RAW cells and endotoxemia-induced I-TAC expression in lung and small intestine. The structural and regulatory similarities of murine and human I-TAC suggest that mouse models will be useful for investigating the role of this chemokine in human biology and disease.
Widney
D P
DP
Department of Pediatrics, University of California, Los Angeles, School of Medicine, 90095, USA.
Xia
Y R
YR
Lusis
A J
AJ
Smith
J B
JB
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000276:immunology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D003907:Dexamethasone / Q000494:pharmacology*; D019446:Endotoxemia / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515203:Cxcl11 protein, mouse; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma