Polydatin Ameliorated Colonic Inflammation via Precluding Phosphorylation of PKCθ/STAT3 Pathway to Inhibit Th17 Cells in Mice with Ulcerative Colitis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect of polydatin on ulcerative colitis （UC） in mice and its regulation of protein kinase C<italic>θ</italic>（PKC<italic>θ</italic>）/signal transducer and activator of transcription 3（STAT3） signaling on T helper cell 17（Th17） and its mechanism in the treatment of UC. Method:The 32 male C57BL/6 mice were randomly divided into normal group， model group， polydatin group （0.045 g·kg^-1） and sulfasalazine group （0.5 g·kg^-1）. The UC model was established by giving 3% dextran sodium sulfate （DSS） solution to free drinking water in mice. Polydatin and sulfasalazine groups were given by gavage 0.5 h before modeling for 7 days. The normal group and model group were given the same amount of normal saline. After the last administration， the colonic tissue was taken and hematoxylin-eosin （HE） was used to observe the pathological changes of colonic tissue. Flow cytometry was used to detect the proportion of Th17 in the lamina propria of colonic mucosa. The expression of interleukin-17A （IL-17A） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Polydatin was added to CD4⁺T cells purified from spleen of C57BL/6 mice by magnetic-activated cell sorting （MACS） under the stimulation of cell stimulation cocktail <italic>in vitro </italic>in order to detect its impact on PKC<italic>θ</italic> and STAT3 phosphorylation. Result:Compared with normal group， the body weight was significantly decreased， and disease activity index （DAI） scores of the model group was significantly increased （<italic>P</italic><0.01）， the colonic mucosal epithelium was damaged and inflammatory cells infiltration in the mucosa and submucosa was obvious， the proportion of Th17 in the lamina propria of colonic mucosa was significantly increased （<italic>P</italic><0.01）， and the content of serum IL-17A was significantly increased （<italic>P</italic><0.01）. Compared with the model group， the weight and DAI score of polydatin and sulfasalazine groups were significantly improved （<italic>P</italic><0.01）， the degree of colon tissue damage was significantly improved， the proportion of Th17 in colon mucosa lamina propria was significantly decreased （<italic>P</italic><0.01）， and the content of IL-17A in serum was significantly decreased （<italic>P</italic><0.01）. <italic>In vitro</italic> experiments showed that polydatin could significantly inhibit the phosphorylation of PKC<italic>θ</italic> and STAT3 in Th17 （<italic>P</italic><0.01） as well as IL-17A secretion. Conclusion:Polydatin can improve the ulcerative colitis in mice via inhibiting the phosphorylation of PKC<italic>θ</italic> and STAT3 to preclude IL-17A secreting in Th17.

Expression of T helper cell 17-related immune factors in women of child bearing age with human papillomavirus subclinical cervical infection / 上海交通大学学报（医学版）

Objective • To investigate the change of immune microenviroment in the lower genital tract of women who had early papillomavirus (HPV) infections. Methods • One hundred and twenty women infected with high-risk HPV were enrolled in the study, who were at the age of 25-46, with no cervical intraepithelial neoplasia (CIN - III ) or cervical carcinoma. Twenty HPV-negative women were used as control, who did not have abnormal cervical squamous epithelial lesions screened by ThinPrep cytologic test. Vagina douche was collected, and the expression of T helper cell 17 (Th17)-related cytokines and interleukin 10 (IL-10)/IL-4 was tested by suspension micro phase protein chip technology. Results • The expression of IL-17, IL-6, TGF-β and IL-4 in HPV-positive patients was significantly higher than that in HPV-negative patients. The expression of IL-4 and IL-10 in HPV16/18-positive patients was significantly lower than that in patients infected with other HPV types. The expression of IL-17, IL-6 and TGF-β in patients with persistent HPV infection was insignificantly higher than that in patients with temporary HPV infection, while the expression of IL-17, IL-6 and TGF-β in patients with persistent HPV infection was significantly higher than that in HPV-negative patients. Conclusion • HPV infection can stimulate the body's immune response and change the local immune microenvironment in early stage. Th17 related cytokines are closely related to the persistent HPV infection. Maybe it can provide a new direction on the guidance of HPV treatment and prevention of persistent HPV infection.