BACKGROUND: In fluorescein isothiocyanate (FITC)-induced contact hypersensitivity models, dibutyl phthalate has been empirically used as a solvent ingredient. We have demonstrated that dibutyl phthalate has an adjuvant effect through the facilitation of trafficking FITC-presenting dendritic cells (DC) from the skin to draining lymph nodes. Here we investigated the effects of local pretreatment with substances that are capable of desensitizing sensory neurons in the sensitization phase. METHODS: Local pretreatment of BALB/c mice with capsaicin (epicutaneous), allyl isothiocyanate (epicutaneous) or a truncated form of calcitonin gene-related peptide (CGRP(8-37); intradermal) was performed before contact sensitization to FITC. The ear swelling test was employed to monitor sensitization. The appearance of FITC-presenting CD11c-positive cells in the draining lymph nodes was detected by flow cytometry. Cytokine production in local lymph node cell cultures was determined by ELISA. RESULTS: The ear swelling response was reduced in mice pretreated with capsaicin or allyl isothiocyanate. DC trafficking and maturation (based on the levels of co-stimulators CD80 and CD86) were inhibited. Interleukin-4 production by local lymph nodes was suppressed with allyl isothiocyanate but not with capsaicin. Pretreatment with CGRP(8-37) suppressed sensitization to FITC. CONCLUSIONS: Local pretreatment with substances that are capable of desensitizing sensory neurons through the respective transient receptor potential channels suppressed skin sensitization to FITC in a mouse model. This was associated with reduced trafficking and maturation of FITC-presenting DC. A CGRP antagonist also suppressed the sensitization to FITC, suggesting the possible involvement of sensory neurons in sensitization.
BACKGROUND: In fluorescein isothiocyanate (FITC)-induced contact hypersensitivity models, dibutyl phthalate has been empirically used as a solvent ingredient. We have demonstrated that dibutyl phthalate has an adjuvant effect through the facilitation of trafficking FITC-presenting dendritic cells (DC) from the skin to draining lymph nodes. Here we investigated the effects of local pretreatment with substances that are capable of desensitizing sensory neurons in the sensitization phase. METHODS: Local pretreatment of BALB/c mice with capsaicin (epicutaneous), allyl isothiocyanate (epicutaneous) or a truncated form of calcitonin gene-related peptide (CGRP(8-37); intradermal) was performed before contact sensitization to FITC. The ear swelling test was employed to monitor sensitization. The appearance of FITC-presenting CD11c-positive cells in the draining lymph nodes was detected by flow cytometry. Cytokine production in local lymph node cell cultures was determined by ELISA. RESULTS: The ear swelling response was reduced in mice pretreated with capsaicin or allyl isothiocyanate. DC trafficking and maturation (based on the levels of co-stimulators CD80 and CD86) were inhibited. Interleukin-4 production by local lymph nodes was suppressed with allyl isothiocyanate but not with capsaicin. Pretreatment with CGRP(8-37) suppressed sensitization to FITC. CONCLUSIONS: Local pretreatment with substances that are capable of desensitizing sensory neurons through the respective transient receptor potential channels suppressed skin sensitization to FITC in a mouse model. This was associated with reduced trafficking and maturation of FITC-presenting DC. A CGRP antagonist also suppressed the sensitization to FITC, suggesting the possible involvement of sensory neurons in sensitization.
Authors: Min-Hee Oh; Sun Young Oh; Jingning Lu; Hongfei Lou; Allen C Myers; Zhou Zhu; Tao Zheng Journal: J Immunol Date: 2013-10-18 Impact factor: 5.422
Authors: Katrin Kistner; Norbert Siklosi; Alexandru Babes; Mohammad Khalil; Tudor Selescu; Katharina Zimmermann; Stefan Wirtz; Christoph Becker; Markus F Neurath; Peter W Reeh; Matthias A Engel Journal: Sci Rep Date: 2016-06-30 Impact factor: 4.379