Modulation of the chemokines KC and MCP-1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice.
Activation of the aryl hydrocarbon receptor (AhR) by TCDD may lead to the induction of proinflammatory cytokines in various cell types and organs such as liver leading to active chronic inflammation. Here we studied the expression of the chemokines keratinocyte chemoattractant (KC) and monocyte chemoattractant protein 1 (MCP-1) in different organs of mice after exposure to TCDD. TCDD exposure led to an early and clear induction of KC in liver and spleen on day 1 which was sustained over a period of 10 days. The level of MCP-1 mRNA was induced by TCDD on day 1 in spleen, lung, kidney, and liver, which was further increased at day 7. Increase of KC and MCP-1 at day 7 in liver, thymus, kidney, adipose, and heart was associated with elevated levels of the macrophage marker F4/80, indicating the infiltration of macrophages in these organs. Induction of KC requires a functional AhR since mice with a mutation in the AhR nuclear localization domain (AhR(nls)) were found to be resistant to TCDD-induced expression of KC. These results are the first showing the induction of the chemokines KC and MCP-1 in multiple organs of mice associated with an increase of the macrophage marker F4/80 indicating the involvement in TCDD's inflammatory response like infiltration of macrophages.
Vogel
Christoph Franz Adam
CF
Department of Environmental Toxicology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA. cfvogel@ucdavis.edu <cfvogel@ucdavis.edu>
Nishimura
Noriko
N
Sciullo
Eric
E
Wong
Patrick
P
Li
Wen
W
Matsumura
Fumio
F
D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology* / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon