title: TRPA1 contributes to the acute inflammatory response and mediates carrageenan-induced paw edema in the mouse.
abstract: Transient receptor potential ankyrin 1 (TRPA1) is an ion channel involved in thermosensation and nociception. TRPA1 is activated by exogenous irritants and also by oxidants formed in inflammatory reactions. However, our understanding of its role in inflammation is limited. Here, we tested the hypothesis that TRPA1 is involved in acute inflammatory edema. The TRPA1 agonist allyl isothiocyanate (AITC) induced inflammatory edema when injected intraplantarly to mice, mimicking the classical response to carrageenan. Interestingly, the TRPA1 antagonist HC-030031 and the cyclo-oxygenase (COX) inhibitor ibuprofen inhibited not only AITC but also carrageenan-induced edema. TRPA1-deficient mice displayed attenuated responses to carrageenan and AITC. Furthermore, AITC enhanced COX-2 expression in HEK293 cells transfected with human TRPA1, a response that was reversed by HC-030031. This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Lauri J
authors.initials: LJ
authors.lastname: Moilanen
authors.forename: Mirka
authors.initials: M
authors.lastname: Laavola
authors.forename: Meiju
authors.initials: M
authors.lastname: Kukkonen
authors.forename: Riku
authors.initials: R
authors.lastname: Korhonen
authors.forename: Tiina
authors.initials: T
authors.lastname: Leppänen
authors.forename: Edward D
authors.initials: ED
authors.lastname: Högestätt
authors.forename: Peter M
authors.initials: PM
authors.lastname: Zygmunt
authors.forename: Riina M
authors.initials: RM
authors.lastname: Nieminen
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D057809:HEK293 Cells; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011687:Purines / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000502:physiology*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D011687:Purines; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002351:Carrageenan; D007052:Ibuprofen