The murine neutrophil-chemoattractant chemokines LIX, KC, and MIP-2 have distinct induction kinetics, tissue distributions, and tissue-specific sensitivities to glucocorticoid regulation in endotoxemia.
Lipopolysaccharide-induced CXC chemokine (LIX) is a novel murine neutrophil-chemoattractant CXC chemokine cloned as a glucocorticoid-attenuated response gene. We investigated LIX message expression in an acute endotoxemia model. LIX message peaks later than KC or macrophage inflammatory protein-2 (MIP-2) and remains elevated longer in almost all tissues. Induced LIX message expression in heart is 5- to 6-fold greater than in lung and spleen, and 20-fold greater than in liver. In contrast, KC expression is equal in heart, lung, and liver, whereas MIP-2 expression is strongest in the lung. Glucocorticoid regulation of these genes also differs. Endotoxemia-induced LIX message expression in the lung is markedly enhanced in adrenalectomized mice and strongly attenuated by dexamethasone, whereas lung KC and MIP-2 expression are unaffected by glucocorticoids. It is surprising to note that endotoxemia-induced brain expression of LIX (but not KC or MIP-2) is increased by dexamethasone. These observations suggest that LIX may have biological roles distinct from KC and MIP-2.
Department of Pediatrics, University of California at Los Angeles School of Medicine 90095-1752, USA.
L E
LE
Rovai
H R
HR
Herschman
J B
JB
Smith
D000208:Acute Disease; D000315:Adrenalectomy; D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D054365:Chemokine CXCL5; D018925:Chemokines; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics*; D002630:Chemotactic Factors / Q000235:genetics; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D019446:Endotoxemia / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics*; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D054365:Chemokine CXCL5; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C094739:Cxcl5 protein, mouse; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D015846:Monokines; D011994:Recombinant Proteins; C074302:keratinocyte-derived chemokines; D003907:Dexamethasone