We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
P2 X7 receptor is required for neutrophil accumulation in a mouse model of irritant contact dermatitis.
- Authors
Silva, Gabriela L.; Sperotto, Nathalia D. M.; Borges, Thiago J.; Bonorino, Cristina; Takyia, Cristina M.; Coutinho‐Silva, Robson; Campos, Maria M.; Zanin, Rafael F.; Morrone, Fernanda B.
- Abstract
Irritant contact dermatitis ( ICD) is an inflammatory reaction caused by chemical toxicity on the skin. The P2 X7 receptor ( P2 X7 R) is a key mediator of cytokine release, which recruits immune cells to sites of inflammation. We investigated the role of P2 X7 R in croton oil ( Cr O)-induced ICD using in vitro and in vivo approaches. ICD was induced in vivo by Cr O application on the mouse ear and in vitro by incubation of murine macrophages and dendritic cells ( DCs) with Cr O and ATP. Infiltrating cells were identified by flow cytometry, histology and myeloperoxidase ( MPO) determination. Effects of the ATP scavenger apyrase were assessed to investigate further the role of P2 X7 R in ICD. Animals were also treated with N-1330, a caspase-1 inhibitor, or with clodronate, which induces macrophage apoptosis. Cr O application induced severe inflammatory Gr1+ cell infiltration and increased MPO levels in the mouse ear. Selective P2 X7 R antagonism with A438079 or genetic P2 X7 R deletion reduced the neutrophil infiltration. Clodronate administration significantly reduced Gr1+ cell infiltration and local IL-1β levels. In vitro experiments confirmed that A438079 or apyrase treatment prevented the increase in IL-1β that was evoked by macrophage and DC incubation with Cr O and ATP. These data support a key role for P2 X7 in ICD-mediated inflammation via modulation of inflammatory cells. It is tempting to suggest that P2 X7 R inhibition might be an alternative ICD treatment.
- Publication
Experimental Dermatology, 2013, Vol 22, Issue 3, p184
- ISSN
0906-6705
- Publication type
Academic Journal
- DOI
10.1111/exd.12094