TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity.
We have revealed that local stimulation of sensory neurons is involved in the adjuvant effect of dibutyl phthalate (DBP) in a fluorescein isothiocyanate-induced mouse contact hypersensitivity model. Transient receptor potential (TRP) A1 and TRPV1 seemed to be candidate DBP targets. Here we directly demonstrated that DBP activates a subset of neurons in mouse dorsal root ganglia responsive to TRPA1 and TRPV1 agonists. TRPA1 and TRPV1 activation was further demonstrated using cultured cells expressing TRP channels. Among structurally different phthalate esters, there is a positive relationship between the activation of TRPA1- or TRPV1-expressing cells and the adjuvant effect.
Shiba
Takahiro
T
Laboratory of Microbiology and Immunology and the Global COE Program, University of Shizuoka Graduate School of Pharmaceutical Sciences, Shizuoka 422-8526, Japan.
Maruyama
Takashi
T
Kurohane
Kohta
K
Iwasaki
Yusaku
Y
Watanabe
Tatsuo
T
Imai
Yasuyuki
Y
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003993:Dibutyl Phthalate / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000209:etiology / Q000473:pathology; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000009:adverse effects; D005456:Fluorescent Dyes / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017879:Isothiocyanates / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010968:Plasticizers / Q000494:pharmacology; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*
D005456:Fluorescent Dyes; D017879:Isothiocyanates; D010968:Plasticizers; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D003993:Dibutyl Phthalate; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D016650:Fluorescein-5-isothiocyanate; D002211:Capsaicin; D002118:Calcium