Nasal administration of autoantigens has been used to treat autoimmune diseases in animals and in humans [19,20]
Nasal administration of autoantigens has been used to treat autoimmune diseases in animals and in humans [19,20]. GST group, five of eight mice in CD36 the PBS group, two of eight mice in the -fodrin 1 g/dose group, and three out of eight mice in the -fodrin 10 g/dose were positive for antinuclear antibodies. The levels of serum IFN in mice immunized with 1 g/dose or 10 g/dose -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 -fodrin groups compared with the PBS and GST control groups ( em P /em 0.05). Lymphocytic infiltration and expression of -fodrin in the salivary glands was decreased in -fodrin-treated groups. The fluid intake of mice in the 1 g/dose -fodrin, 10 g/dose -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, Myelin Basic Protein (87-99) respectively. Conclusion Mucosal administration of -fodrin effectively inhibited the progression of experimental Sj?gren’s syndrome autoimmunity. Introduction Main Sj?gren’s syndrome (SS) is a chronic autoimmune disorder of unknown etiology. Lymphocytic infiltration of the lachrymal and salivary glands prospects to dry mouth (xerostomia) and dry eyes (xerophthalmia). It has been assumed that a combination of immunologic, genetic, and environmental factors plays an important role in the development of autoimmune abnormalities Myelin Basic Protein (87-99) in main SS. In 1997 Haneji and colleagues recognized a 120 kDa fragment of the ubiquitous cytoskeletal protein -fodrin as an autoantigen in the NFS/sld mouse model of human SS . It has been shown by immunoblotting that anti–fodrin antibodies are present in sera from 93% of main SS patients and from 63% of secondary SS patients, but not in sera from systemic lupus erythematosus (SLE) patients or rheumatoid arthritis patients and normal control individuals . In a previously published study we reported comparable results, finding that these antibodies are positively correlated with the systemic manifestation of SS [2,3]. em In vivo /em functions of -fodrin N-terminal portion peptides were investigated using peripheral blood mononuclear cells from patients with SS, from patients with SLE, and from patients with rheumatoid arthritis. Significant proliferative T-cell responses of peripheral blood mononuclear cells o -fodrin peptide were detected in SS but not in SLE or rheumatoid arthritis . We previously recognized em in vivo /em immunoregulation of -fodrin using the same method. Kurien and colleagues experienced induced oral tolerance in experimental SS animal successfully . There have been other reports of nasal and oral tolerance in SS [6,7], a phenomenon that brings about systemic immune hyporesponsiveness by Myelin Basic Protein (87-99) the exogenous administration of antigen to the peripheral immune system through the mucosal route. We hypothesized that nasal tolerance could be induced in an experimental animal model of SS by nasal administration of -fodrin, potentially preventing and inhibiting the development of SS. The present study was undertaken in order to test this hypothesis. Materials and methods Materials The plasmid (pGEX-4T-2C-fodrin) was a nice gift from Professor Hayashi of the Tokushima University School of Dentistry in Japan. Large-scale bacterial expression and fusion protein purification A 5 ml saturated culture of pGEX-4T-2C-fodrin-transformed bacteria produced in Luria-Bertani(LB) medium supplemented with ampicillin (100.