| First Author | Xu B | Year | 2003 |
| Journal | Int Immunopharmacol | Volume | 3 |
| Issue | 7 | Pages | 927-38 |
| PubMed ID | 12810350 | Mgi Jnum | J:106217 |
| Mgi Id | MGI:3617749 | Doi | 10.1016/S1567-5769(03)00081-X |
| Citation | Xu B, et al. (2003) Role of Fas/Fas ligand-mediated apoptosis in murine contact hypersensitivity. Int Immunopharmacol 3(7):927-38 |
| abstractText | Apoptosis plays an important role in immune responses, but little is known about its involvement in contact hypersensitivity (CH). In this study, we have investigated the role of Fas/Fas ligand (FasL)-mediated apoptosis in the pathogenesis of CH. Mice were sensitized by one topical application of 100 microl of 3% oxazolone to shaved skin of the abdomen. Six days later, CH was provoked by challenging both sides of sensitized mouse right ear with 15 microl of 1% oxazolone. Using a DNA ladder assay, we found that apoptosis was induced in the skin of oxazolone-sensitized mice 24-96 h after allergen challenge. Annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) apoptosis flow cytometric assay showed that early apoptotic CD4(+) T cells (annexin V-FITC(+)PI(-)), but not late apoptotic CD4(+) T cells (annexin V-FITC(+)PI(+)), increased in the inflamed skin of mice with CH. Moreover, the expressions of mRNAs for T helper (Th2) cytokine (interleukin (IL)-4), Th1 cytokine (interferon (IFN)-gamma) and proapoptotic molecules (Bax, Fas, FasL and IL-1beta-converting enzyme (ICE)/caspase-1) were significantly elevated in the oxazolone-sensitized mouse skin 6-72 h after allergen challenge. Dramatic increase in IL-10 mRNA was only observed in the sensitized mouse skin 6 and 12 h after allergen challenge. Furthermore, CH was significantly inhibited with decreased apoptosis and early apoptotic CD4(+) T cells in inflamed skin in Fas mutant lpr/lpr mice compared to wild-type mice, whereas there were no significant differences in IL-4, IFN-gamma, IL-10, Bax and ICE mRNAs in the inflamed skin of CH between lpr/lpr and wild-type mice. Our results thus suggest that Fas/FasL pathway partially contributes to apoptosis in murine CH and that Fas/FasL-mediated apoptosis plays a partial role in the development of CH. The contribution of Fas/FasL-mediated apoptosis to CH appears independent of Th1 and Th2 cytokines. |
