The role of kinin B-1 and B-2 receptors in the mouse model of oxazolone-induced atopic dermatitis

摘要

This study evaluated the role of kinin B-1 and B-2 receptors in the pre-clinical mouse model of oxazolone-induced atopic dermatitis. The B-1 R715 or B-2 HOE140 receptor antagonists were dosed at different schemes of treatment. After assessment of clinical lesion scores and pruritus, lesional skin samples were collected for histopathological analysis. The plasma extravasation and the expression of the metalloproteinase ADAMTS5 were also assessed. The immunopositivity for kinin receptors was evaluated in the skin, dorsal root ganglion (DRG), thoracic spinal cord and brain cortex sections. Marked upregulation of B-1 and B-2 receptors was observed in the skin of oxazolone-treated mice. The induction of atopic dermatitis led to a downregulation of both receptors in the DRG, without any alteration in the spinal cord and brain cortex. The repeated administration of HOE140 (50 nmol/kg; i.p.) partially inhibited the oxazolone-related pruritus, associated with a reduction of ADAMTS5 immunolabelling in the skin. Alternatively, R715 (438 nmol/kg; i.p.) produced a mild inhibition of plasma extravasation in oxazolonechallenged mice. Noteworthy, the repeated i.d. injection of R715 (30 nmol/site) or HOE140 (3 nmol/site) significantly reduced the histiocyte numbers, according to the histopathological analysis. Either B-1 or B-2 kinin antagonists, irrespective of the protocol of treatment, did not alter any other evaluated clinical or histological parameters. Data brings novel evidence about the role of kinin receptors in allergy-related conditions, such as atopic dermatitis. Further studies to test different protocols of treatment with kinin antagonists on in-depth cellular alterations underlying oxazolone-induced atopic dermatitis remain to be performed.