Objective To investigate the immunoregulatory effect of Fasudil-modified macrophages on cell transferred experimental autoimmune encephalomyelitis ( EAE) in a mouse model.Methods Fe-male C57BL/6 mice were immunized with MOG35-55 to establish the model of EAE.The encephalomyelitic mononuclear cells ( MNCs) were isolated from spleen of mice with EAE on day 9 after immunization and treated with or without Fasudil for 72 h in vitro.Several assays including the flow cytometry analysis, Griess reaction and ELISA were performed to analyze the M1 and M2 phenotypes of macrophages, the production of NO and the levels of cytokines, respectively.The cultured MNCs (5×107 cells) were resuspended in 500μl of PBS and transferred into na?ve C57BL/6 recipients via intraperitoneal injection.Two groups including the PBS-MNCs group and the Fasudil-MNCs group were set up.The body weights and clinical scores of the mice in each group were recorded in every other days after the induction of EAE in the recipients.Results The Fasudil treated MNCs affected the induction of EAE in adoptive cell transferred mice.The expression of CD16/32, iNOS and IL-12 on F4/80-macrophages were decreased, while the expression of CD206, CD23 and IL-10 on F4/80-macrophages were increased upon the treatment of Fasudil, indicating that Fasudil im-proved the differentiation of macrophages from M1 to M2 phenotypes.Moreover, Fasudil inhibited the pro-duction of NO and enhanced the expression of Arginase-1.Conclusion Fasudil ameliorated the clinical se-verity of EAE in mice by promoting the transformation of macrophages from M1 to M2 phenotype.

OBJECTIVE: To discuss the disease incidence of bronchial asthma (BA) complicated with allergic rhinitis (AR) and the correlation of their age, classification, concomitant symptom. METHOD: Four hundred-nine cases of AR were identified by means of random sampling, physical examination, laboratory test and questionnaire. According to the diagnostic criteria of BA, they were divided into two groups: group I ( control group) including 298 cases suffering from only AR, group II ( experimental group) 191 cases of BA concomittent with AR. RESULT: 1) This study showed that BA concomittent with AR account for 39% of all cases; 2) Incidence of aspirin triad syndrome (asthma, rhinopolyps and aspirin intolerance) was significantly different in two groups (P<0.01); 3) As for age group distribution, there was significant difference between groups in age segment 10-19 and 40-49 (P<0.05); 4) Disease classification: there were significant differences in the incidence of moderate to severe intermittent AR, mild continuous AR, and moderate to severe continuous AR between two groups (P<0.05); 5) Other major concomitant diseases and symptoms distribution; the concomittant occurrence of allergic pharyngitis, sinusitis, conjunctivitis, secretory tympanitis, hypertrophic rhinitis, dermatosis, discomfort of gastrointestinal tract, and headache of unknown origin were significantly different between two groups (P<0.05). The difference above showed that the occurrence in experimental group was higher than that in control group. CONCLUSION the incidence of BA complicated with AR were relatively high in Datong, with a peak incidence at age 10 to 19 and 40 to 49. The common types of disease were moderate to severe intermittent AR, mild continuous AR, and moderate to severe continuous AR. The number of patients with BA complicated with AR were growing.
Adolescent ; Adult ; Aged ; Asthma ; complications ; epidemiology ; Child ; China ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Rhinitis, Allergic, Perennial ; complications ; epidemiology ; Rhinitis, Allergic, Seasonal ; complications ; epidemiology ; Surveys and Questionnaires ; Young Adult

OBJECTIVE: To explore the therapeutic effect of Fasudil-modified splenic mononuclear cells (MNCs) in experimental autoimmune encephalomyelitis (EAE) and the possible mechanisms.
 METHODS: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 to establish active immunity EAE model. Splenic MNCs were isolated on the 9th day after immunization and treated with or without Fasudil for 72 h in vitro. These cells were collected for analysis of the variance of T cell subtypes, the level of cytokines and the activity of Rho kinase (ROCK). MNCs (5×107 cells) were resuspended in 500 µL of phosphate buffer solution (PBS) and transferred into EAE model (intraperitoneal injection), which was divided into a PBS-MNCs group and a Fasudil-MNCs group. Changes of body weight and clinical symptom scores were observed.
 RESULTS: Splenic encephalitogenic MNCs from EAE mice on the 9th day after immunization could establish passive transfer EAE model. But Fasudil-treated MNCs did not trigger EAE development. Compared with the PBS-MNCs group, the loss of body weight was less in the Fasudil-MNCs group. The in vitro experiment indicated that Fasudil could suppress the activity of ROCK on MNCs (P<0.01), decrease the percentage of CD4+ T cells with the expression of interferon-γ (IFN-γ) and interleukin-17 (IL-17) (IFN-γ: P<0.01; IL-17: P<0.05), while increase the secretion of CD4+ T cells with the expression of transforming growth factor-β (TGF-β) and IL-10 (all P<0.001) . Furthermore, Fasudil could inhibit the release of IL-17 (P<0.001) and enhance the level of IL-10 (P<0.05).
 CONCLUSION Fasudil-modified cell therapy affects the occurrence and development of EAE by inhibiting the inflammatory reaction of helper T cell 1 (Th1) and Th17 while enhancing the immunoregulative effect of Th2.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; Animals ; Encephalomyelitis, Autoimmune, Experimental ; Female ; Interferon-gamma ; Interleukin-10 ; Interleukin-17 ; Mice ; Mice, Inbred C57BL ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; T-Lymphocytes ; Transforming Growth Factor beta ; rho-Associated Kinases