title: Involvement of leukotriene B4 in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions.
abstract: To elucidate the mechanisms of severe itch in atopic dermatitis, we investigated the role of leukotriene B(4) , a potent itch mediator, in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions. Topical application of the BLT leukotriene B(4)  receptor antagonist ONO-4057 inhibited spontaneous itch-related behaviour. The concentration of leukotriene B(4)  was significantly increased in the lesional skin. The expression levels of 5-lipoxygenase were also elevated in the lesional skin, yet present throughout the epidermis of both healthy and lesional skin. These results suggest a role for leukotriene B(4)  in chronic dermatitis-related itch. Sphingosylphosphorylcholine (SPC) was increased in the epidermis of the lesional skin. Moreover, intradermal injection of SPC elicited itch-related behaviours in healthy mice. Because SPC induces itch-related responses through the production of leukotriene B(4)  in keratinocytes (J Invest Dermatol, 129, 2009, 2854), these results suggest that an increase in SPC induces leukotriene B(4) -mediated itching in chronic dermatitis. BLT1 receptor and 5-lipoxygenase in the skin may be effective pharmacological targets for the treatment of itch in atopic dermatitis.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Satomi
authors.initials: S
authors.lastname: Haza
authors.forename: Ayumi
authors.initials: A
authors.lastname: Saito
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D007975:Leukotriene B4 / Q000502:physiology*; D051379:Mice; D010666:Phenylpropionates / Q000008:administration & dosage; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D011537:Pruritus / Q000209:etiology* / Q000503:physiopathology; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D012867:Skin / Q000187:drug effects / Q000503:physiopathology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C503704:Ltb4r1 protein, mouse; D010666:Phenylpropionates; D018102:Receptors, Leukotriene B4; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C067523:ONO-LB 457; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D013110:Sphingosine