Phthalate ester-induced thymic stromal lymphopoietin mediates allergic dermatitis in mice.
Recently air pollutants and irritants have been labelled as possible exogenous risk factors for allergic disorders. Although the underlying causes of allergic disorders such as atopic dermatitis and asthma remain unclear, the T helper type 2 (Th2) cell-mediated allergic inflammatory cascade may contribute to their pathogenesis. In the last decade, it has been documented that one of the candidates for triggering Th2 commitment is thymic stromal lymphopoietin (TSLP), the expression of which is up-regulated in the lesions of allergic patients. Here, we describe TSLP function in a fluorescein isothiocyanate (FITC) -induced contact hypersensitivity (CHS) model. A cytokine profile indicated that the model was dominantly mediated by the Th2 milieu. Interestingly, TSLP was increased in the skin during the sensitization phase when stimulated by a solvent, dibutyl phthalate (DBP), but not by FITC hapten or another solvent, acetone. Ear swelling in FITC-induced CHS was totally abrogated by removing DBP from the sensitization or elicitation phase, and was restored by complementary injection of TSLP. Inversely, the ear swelling was suppressed by injection of small interfering RNA against TSLP during the sensitization phase, which was concomitant with decreasing expression of interleukin-4 at the swollen skin site. Taken together, DBP-induced TSLP during the sensitization phase plays a role in establishing FITC-induced CHS and may be one of the causes of Th2 commitment in the model, suggesting that certain environmental toxins, such as DBP, may endow pro-allergic and atopic predisposition in humans or animals.
Shigeno
Tomomi
T
Drug Discovery Research, Kyoto R&D Centre, Maruho Co., Ltd, Chudoji, Kyoto, Japan.
Katakuse
Mayako
M
Fujita
Tomoyuki
T
Mukoyama
Yohei
Y
Watanabe
Hideki
H
D000485:Allergens / Q000276:immunology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D003993:Dibutyl Phthalate / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry / Q000494:pharmacology*; D020868:Gene Silencing; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000276:immunology; D012997:Solvents / Q000737:chemistry / Q000494:pharmacology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D016207:Cytokines; D034741:RNA, Small Interfering; D012997:Solvents; D015847:Interleukin-4; D003993:Dibutyl Phthalate; D007073:Immunoglobulin E; D016650:Fluorescein-5-isothiocyanate; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse