| Title | Mucosal administration of alpha-fodrin inhibits experimental Sjogren's syndrome autoimmunity |
| Authors | He, Jing Zhao, Jinxia Li, Zhanguo |
| Affiliation | Peking Univ, Peoples Hosp, Dept Rheumatol Immunol, Sch Med, Beijing 100044, Peoples R China. Peking Univ, Peoples Hosp, Dept Rheumatol Immunol, Sch Med, 11 Xizhimen S St, Beijing 100044, Peoples R China. |
| Keywords | DENDRITIC CELLS ORAL TOLERANCE NOD MOUSE AUTOANTIBODIES AUTOANTIGEN MICE ANTIBODIES MECHANISMS PEPTIDE NASAL |
| Issue Date | 2008 |
| Publisher | 关节炎研究与治疗 |
| Citation | ARTHRITIS RESEARCH & THERAPY.2008,10,(2). |
| Abstract | Introduction alpha-Fodrin is an autoantigen in Sjogren's syndrome. We hypothesized that mucosal administration of alpha-fodrin might prevent the disease. Methods Four-week-old NOD mice were immunized (intranasal) with a 1 mu g or 10 mu g dose of alpha-fodrin every other day. PBS 10 mu l/dose and Glutathione transferase (GST 10 mu g/dose (control mice) were intranasally administrated by the same procedure. The salivary flow was maintained in immunized animals. The animals were analyzed for the presence of anti-Sjogren's syndrome A, anti-Sjogren's syndrome B, rheumatoid factor and antinuclear, anti-alpha-fodrin, and anti-type 3 muscarinic acetylcholine receptor polypeptide (anti-M3RP) by immunofluorescence or ELISA. The cytokines IFN gamma and IL-10 were measured by ELISA. Salivary glands were examined by H& E staining and immunohistochemical analysis. The water-volume intake was calculated for each group. The induction of regulatory T cells was assessed by fluorescence-activated cell sorting analysis for the frequency of Foxp3(+) cells among peripheral CD4(+) CD25(+) T cells. Results The appearance of anti-alpha-fodrin and anti-M3RP antibodies was delayed in mice immunized with alpha-fodrin. The titers of anti-alpha-fodrin and anti-M3RP antibodies were lower in immunized mice (P < 0.05), but there was no significant difference between the low-dose or high-dose immunization groups. Five out of eight mice in the GST group, five of eight mice in the PBS group, two of eight mice in the alpha-fodrin 1 mu g/dose group, and three out of eight mice in the alpha-fodrin 10 mu g/dose were positive for antinuclear antibodies. The levels of serum IFN gamma in mice immunized with 1 mu g/dose or 10 mu g/dose alpha-fodrin,with PBS, and with GST were 41.9 +/- 16.2 pg/ml, 37.1 +/- 15.4 pg/ml, 86.8 +/- 17.8 pg/ml and 71.6 +/- 11.1 pg/ml, respectively, while we found no difference in the levels of serum IL-10 among the groups. The number of Foxp3(+) CD4(+) CD25(+) regulatory T cells was higher in the alpha-fodrin groups compared with the PBS and GST control groups (P < 0.05). Lymphocytic infiltration and expression of alpha-fodrin in the salivary glands was decreased in alpha-fodrin-treated groups. The fluid intake of mice in the 1 mu g/dose alpha-fodrin, 10 mu g/dose mu-fodrin, PBS, and GST groups was 39.2 +/- 2.1 ml, 40.4 +/- 2.5 ml, 49.3 +/- 3.1 ml and 51.6 +/- 2.8 ml, respectively. Conclusion Mucosal administration of alpha-fodrin effectively inhibited the progression of experimental Sjogren's syndrome autoimmunity. |
| URI | http://hdl.handle.net/20.500.11897/159624 |
| ISSN | 1478-6354 |
| DOI | 10.1186/ar2403 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 人民医院 |
