Inhibition of Mast Cell Degranulation in Atopic Dermatitis by Celastrol through Suppressing MRGPRX2.

Background: Atopic dermatitis is a common dermatological disease, and mast cell degranulation is believed to be related with the progression of atopic dermatitis. Mas-related G protein-coupled receptor-X2 (MRGPRX2), and calcium release-activated calcium channel protein 1-2 (ORAI-1, ORAI-2) are involved in mast cell degranulation. Celastrol is an active monomer of Tripterygium wilfordii, and it presents an antiatopic role. Methods: 2,4-Dinitrofluorobenzene (DNFB) and compound 48/80 (C 48/80) were used to establish a slow and acute scratching animal model, respectively. Hematoxylin-eosin and toluidine blue staining was used to investigate tissue injury. Inflammatory factor concentration was measured with ELISA. The expression of MRGPRX2, ORAI-1, and ORAI-2 was detected with immunohistochemistry (IHC) staining. Gene expression profiling and microRNA array were performed to investigate gene differential expression. Results: Celastrol greatly inhibited atopic dermatitis-related tissues injury, mast cell production, histamine release, scratching level, inflammatory factor expression, and activation of MRGPRX2/ORAI axis in the DNFB-induced atopic dermatitis model. The influence of Celastrol on atopic dermatitis was remarkably reversed by overexpression of MRGPRX2. Conclusion: We found that the improvements of atopic dermatitis caused by Celastrol were reversed by treatment with MRGPRX2OE, indicating that Celastrol might affect atopic dermatitis through MRGPRX2. This study might provide a novel thought for the prevention and treatment of atopic dermatitis by regulating MRGPRX2.

Cumulative causation, market transition, and emigration from China.

This article reports findings from a recent survey of international migration from China's Fujian Province to the United States. Using the ethnosurvey approach developed in the Mexican Migration Project, the authors conducted surveys in migrant-sending communities in China as well as in destination communities in New York City. Hypotheses are derived from the international migration literature and the market transition debate. The results are generally consistent with hypotheses derived from cumulative causation of migration; however, geographical location creates some differences in migration patterns to the United States. In China as in Mexico, the existence of migration networks increases the propensity of migration for others in the community. In contrast to the Mexican case, among Chinese immigrants, having a previously migrated household member increases the propensity of other household members to migrate only after the debt for previous migration is paid off. In step with market transition theory, the authors also find that political power influences the migration experience from the coastal Fujian Province.