| First Author | Scholzen TE | Year | 2004 |
| Journal | FASEB J | Volume | 18 |
| Issue | 9 | Pages | 1007-9 |
| PubMed ID | 15084523 | Mgi Jnum | J:118457 |
| Mgi Id | MGI:3699639 | Doi | 10.1096/fj.03-0658fje |
| Citation | Scholzen TE, et al. (2004) Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage. FASEB J 18(9):1007-9 |
| abstractText | Sensory neuropeptides such as neurokinin A (NKA) or particularly substance P (SP) by neurokinin receptor (NK-R) activation modulate skin and immune cells functions during neurogenic inflammation. In this study, we examined the relative importance of SP/NK-1Rs or NKA/NK-2Rs in a murine model for allergic contact dermatitis (ACD) and tested if the functional absence of NK-Rs will impair inflammatory response in vivo. Mice lacking NK-1Rs (C57BL/6J-NK-1R-/-) displayed a significantly reduced ACD inflammatory ear swelling response to dinitrofluorobenzene (DNFB) with histological less edema and 50% fewer infiltrating leukocytes compared with the ACD response in wild-type (+/+) animals. In NK-1R+/+ mice, transient NK-1R inhibition impaired ACD sensitization. In vitro haptenized bone marrow-derived dendritic cells from NK-1R+/+ mice matured in the presence of an NK-1R antagonist displayed a reduced capability to induce T cell proliferation in vitro and ACD after adoptive transfer into naive wild-type mice in vivo. By contrast, NK-2R inhibition significantly enhanced the ACD response in NK-1R null or in wild-type mice, whereas epicutaneous application of NK-2R agonists diminished the ACD inflammation. In conclusion, NK-1R and SP are required for antigen sensitization and a full inflammatory response to cutaneous allergens and NKA and the NK-2R mediate a contrasting anti-inflammatory role in ACD. Thus, SP, NKA, NK-1R, and NK-2R have important but differential roles in the regulation of cutaneous inflammatory responses. |
