Contact sensitizer 2,4-dinitrochlorobenzene is a highly potent human TRPA1 agonist.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 7804028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1398-9995 (Electronic) Linking ISSN: 01054538 NLM ISO Abbreviation: Allergy Subsets: MEDLINE
    • Publication Information:
      Publication: Copenhagen : Wiley-Blackwell
      Original Publication: Copenhagen, Munksgaard.
    • Subject Terms:
      Dermatitis, Allergic Contact/*immunology ; Dinitrochlorobenzene/*immunology ; Irritants/*immunology ; Nerve Tissue Proteins/*agonists ; Transient Receptor Potential Channels/*agonists; Calcium Channels ; HEK293 Cells ; Humans ; Patch-Clamp Techniques ; TRPA1 Cation Channel
    • Abstract:
      2,4-Dinitrochlorobenzene (DNCB) is widely used in human clinical studies and in experimental animal studies to evoke allergic contact dermatitis. 2,4-Dinitrochlorobenzene is a potent immunogen capable of inducing contact sensitization in all humans exposed. However, the mechanism by which DNCB evokes such symptoms is presently unknown. TRPA1 is a nonselective cation channel that is expressed in peptidergic sensory neurons and fibroblasts. TRPA1 activation was recently implicated in the pathophysiology of atopic dermatitis especially in transducing cutaneous itch signals. Here, we test the hypothesis that DNCB acts as a TRPA1 agonist and thereby evokes allergic symptoms. We found that DNCB activates human TRPA1 dose dependently in FLIPR experiments with an EC50 of 167 nM, an effect that was fully blocked by selective TRPA1 antagonists Chembridge-5861528 and A-967079. Similarly, DNCB activated nonselective TRPA1 current in patch clamp studies. Neutralization of 3 critical cysteines in TRPA1 resulted in a loss of DNCB agonism.
      (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
    • Contributed Indexing:
      Keywords: 2,4-dinitrochlorobenzene; allergic contact dermatitis; allergy; contact hypersensitivity; human TRPA1
    • Accession Number:
      0 (Calcium Channels)
      0 (Dinitrochlorobenzene)
      0 (Irritants)
      0 (Nerve Tissue Proteins)
      0 (TRPA1 Cation Channel)
      0 (TRPA1 protein, human)
      0 (Transient Receptor Potential Channels)
    • Publication Date:
      Date Created: 20140722 Date Completed: 20150514 Latest Revision: 20201209
    • Publication Date:
      20240829
    • Accession Number:
      10.1111/all.12488
    • Accession Number:
      25041656