TRPA1 and CGRP antagonists counteract vesicant-induced skin injury and inflammation.
TRPA1 and CGRP antagonists counteract vesicant-induced skin injury and inflammation.
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DOI：
10.1016/j.toxlet.2018.03.007
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发表时间：
2018-09-01
影响因子：
3.5
通讯作者：
Jordt SE
中科院分区：
文献类型：
--
作者：
Achanta S;Chintagari NR;Brackmann M;Balakrishna S;Jordt SE
The skin is highly sensitive to the chemical warfare agent in mustard gas, sulfur mustard (SM) that initiates a delayed injury response characterized by erythema, inflammation and severe vesication (blistering). Although SM poses a continuing threat, used as recently as in the Syrian conflict, no mechanism-based antidotes against SM are available. Recent studies demonstrated that Transient Receptor Potential Ankyrin 1 (TRPA1), a chemosensory cation channel in sensory nerves innervating the skin, is activated by SM and 2-chloroethyl ethyl sulfide (CEES), an SM analog, in vitro, suggesting it may promote vesicant injury. Here, we investigated the effects of TRPA1 inhibitors, and an inhibitor of Calcitonin Gene Related Peptide (CGRP), a neurogenic inflammatory peptide released upon TRPA1 activation, in a CEES-induced mouse ear vesicant model. TRPA1 inhibitors (HC-030031 and A-967079) and a CGRP inhibitor (MK-8825) reduced skin edema, pro-inflammatory cytokines (IL-1β, CXCL1/KC), MMP-9, a protease implicated in skin damage, and improved histopathological outcomes. These findings suggest that TRPA1 and neurogenic inflammation contribute to the deleterious effects of vesicants in vivo, activated either directly by alkylation, or indirectly, by reactive intermediates or pro-inflammatory mediators. TRPA1 and CGRP inhibitors represent new leads that could be considered for validation and further development in other vesicant injury models.
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影响因子：
3.8
作者：
Brone, Bert;Peeters, Pieter J.;Gijsen, Harrie J. M.
通讯作者：
Gijsen, Harrie J. M.
影响因子：
5.1
作者：
Buech, Thomas Robert Heinrich;Schaefer, Eva Anna Maria;Schmidt, Annette
通讯作者：
Schmidt, Annette
DOI：
10.1152/physiol.00026.2008
发表时间：
2008-12
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Bessac BF;Jordt SE
通讯作者：
Jordt SE
DOI：
10.1111/apha.12442
发表时间：
2015-03
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Granstein RD;Wagner JA;Stohl LL;Ding W
通讯作者：
Ding W
影响因子：
2.7
作者：
Bell, Ian M.;Stump, Craig A.;Salvatore, Christopher A.
通讯作者：
Salvatore, Christopher A.