Regulation of macrophage inflammatory protein-2 gene expression in response to 2,4-dinitrofluorobenzene in RAW 264.7 cells.
Several skin sensitizers, like 2,4-dinitrofluorobenzene (DNFB), are known to provoke contact hypersensitivity responses after topical application. Here, we show that DNFB can upregulate macrophage inflammatory protein-2 (MIP-2) expression in RAW 264.7 cells via a mechanism that is largely dependent on mitogen-activated protein kinase (MAPK) signaling pathways. ELISA-based transcription factor activation assays and chromatin immunoprecipitation assays revealed that functional interaction between AP-1 and MIP-2 promoter element is necessary for MIP-2 gene expression by DNFB. Interestingly, topical application of DNFB to NC/Nga mice increased MIP-2 expression in dermis, suggesting that MIP-2 contributes to the leukocyte infiltration associated with atopic dermatitis. These results provide additional insight of the mechanism of contact hypersensitivity induced by contact sensitizers.
Kim
Dongbum
D
Center for Medical Science Research, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
Kim
Jinho
J
Kwon
Sanghoon
S
Kim
Young-Jin
YJ
Lee
Soohyoung
S
Lee
Younghee
Y
Seo
Jae-Nam
JN
Park
Cheung-Seog
CS
Park
Kui Lea
KL
Kwon
Hyung-Joo
HJ
D000287:Administration, Topical; D000818:Animals; D002460:Cell Line; D054426:Chemokine CXCL2 / Q000235:genetics* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000235:genetics; D020405:Dermis / Q000187:drug effects / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D054426:Chemokine CXCL2; D016755:Proto-Oncogene Proteins c-jun; D004139:Dinitrofluorobenzene; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases