Analysis of differential gene expression in auricular lymph nodes draining skin exposed to sensitizers and irritants.
There has been some concern that certain non-sensitizing irritants may yield false positive results in the murine local lymph node assay (LLNA). This study compared gene expression profiles in lymph nodes draining skin following exposure to sensitizers and irritants, to identify gene transcripts that could distinguish sensitizers from irritants. After treating CBA/N mouse ears for 3 days with the sensitizers 1-chloro-2,4-dinitrobenzene, 2-phenyl-4-ethoxymethylene-5-oxazolone, or toluene-2,4-diisocyanate or the non-sensitizing irritants croton oil or nonanoic acid, auricular lymph nodes and ear tissues were excised. Sensitizer-induced changes in parameters such as ear thickness, lymph node weight, and cell count also occurred in irritant-treated mouse tissues. However, gene transcripts such as Ifi27, Il12rb1, Ifng, and Zbp1, which are related to T-cell activation, were shown by gene expression microarrays and real-time RT-PCR analyses to be up-regulated in auricular lymph nodes by sensitizers exclusively. These findings suggest that gene expression analysis may enable distinction between sensitizing chemicals and non-sensitizing irritants.
Ku
Hyun-Ok
HO
Toxicology and Chemistry Division, National Veterinary Research and Quarantine Service, Anyang, Republic of Korea.
Jeong
Sang-Hee
SH
Kang
Hwan-Goo
HG
Pyo
Hyun-Mi
HM
Cho
Joon-Hyoung
JH
Son
Seong-Wan
SW
Ryu
Doug-Young
DY
D000485:Allergens / Q000145:classification / Q000633:toxicity*; D000818:Animals; D054644:Ear Auricle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D007509:Irritants / Q000145:classification / Q000633:toxicity*; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000485:Allergens; D007509:Irritants; D012333:RNA, Messenger