Thymol activates TRPM8-mediated Ca2+ influx for its antipruritic effects and alleviates inflammatory response in Imiquimod-induced mice
TOXICOLOGY AND APPLIED PHARMACOLOGY
Authors: Wang, Wen; Wang, Hua; Zhao, Zhongqiu; Huang, Xiaoqing; Xiong, Hairong; Mei, Zhinan
Abstract
Psoriasis is a highly prevalent chronic dermatitis, characterized by widespread skin inflammation and spontaneous itch. Given the adverse reactions and drug dependence of current treatment, new drugs for psoriasis therapy are urgently needed. This study aims to explore the anti-psoriatic effects of thymol in imiquimod (IMQ) induced mice, and elucidate the potential mechanisms for its therapeutic activities. Thymol reduced the scratching behavior in IMQ mice, and activated Ca2+ response in cervical DRG neurons via TRPM8 channel. Also, thymol alleviated psoriasis-like skin lesions, and attenuated the enhanced infiltration of dermal neutrophils, dendritic cells (DCs) and Th17 cells. In addition, it reversed the upregulated expression of pro-inflammatory cytokines in the skin (TNF-alpha, IL-22, IL-23, IL-17A, IL-17F, IL-17C, IL-6, IL-1 beta and IFN-gamma) and serum (TNF-alpha, IL-6, IL-1 beta, IL-17A and IFN-gamma). Our results indicated that thymol can effectively ameliorate pruritus and the symptoms of psoriasis-like inflammation induced by IMQ, which makes it a promising drug for the treatment of psoriasis.
The characteristics of CDC+T-helper cell subset differentiation in experimental Clonorchis sinensis-infected FVB mice
IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
Authors: Kong, Delong; Li, Xiangyang; Zhang, Beibei; Yan, Chao; Tang, Renxian; Zheng, Kuiyang
Abstract
Objective(s): Immune responses are tightly regulated in the development of clonorchiasis. However, the adaptive immune regulatory pathway contributing to the pathological processes of clonorchis sinensis (C. sinensis) infection is still not clear. In this study, we assessed the dynamic changes of CD4(+)T cell subsets and the related cytokines as well as transcription factors during C. sinensis infection. Materials and Methods: We used female FVB mice to establish the infection model. H&E and Masson's stain were performed in 2 or 8 weeks post-infection (PI) liver of C. sinensis. The percentages of splenic Th1, Th2, and Treg in CD4+T cells were detected by flow cytometry. The transcription factors T-bet, GATA3, Foxp3, and RORyt gene expression were detected by qPCR. The protein expression of IL-10, IL-17, IL-4, IL-2, and Tumor Necrosis Factor-alpha (TNF-alpha) were examined using ELISA. Results: The percentages of splenic Th1, Th2, and Treg in CD4(+)T cells were significantly increased in both 2 and 8 weeks PI of C. sinensis, while the ratio of Treg/Th17 as well as the percentage of Treg in serum was gradually increased during the development of infection. The expressions of T-bet, GATA3, Foxp3, and ROR gamma t were increased in 8 weeks PI. Serum levels of IL-10, IL-17, IL-4, and IL-2 were profoundly increased in infected mice, while the concentrations of TNF-alpha increased to peak two weeks PI. Conclusion: Our results suggested that the imbalance of CD4(+)T cell subsets may regulate and contribute to an appropriate compromise between pathology, tissue repair, and elimination in a susceptible murine host.