Imiquimod-related dermatitis is mainly mediated by mast cell degranulation via Mas-related G-protein coupled receptor B2
| Autor: | Yongjing Zhang, Langchong He, Delu Che, Hui Han, Shuzhen Kong, Yi Zheng, Jiao Cao, Jihai Shi, Yong Hao, Songmei Geng, Jiapan Gao, Bin Peng, Rui Liu, Jue Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Drug-Related Side Effects and Adverse Reactions medicine.medical_treatment Immunology Dermatitis Imiquimod Pharmacology Cell Degranulation Receptors G-Protein-Coupled Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Immunology and Allergy Calcium Signaling Mast Cells Receptor Mice Knockout Degranulation medicine.disease Mast cell Mice Inbred C57BL Disease Models Animal HEK293 Cells 030104 developmental biology Cytokine medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Contact dermatitis Histamine Intracellular medicine.drug |
| Zdroj: | International Immunopharmacology. 81:106258 |
| ISSN: | 1567-5769 |
| Popis: | While imiquimod (IMQ) has been widely used in dermatology, its side effect manifested as dermatitis couldn't be ignored. However, the underlying mechanism has not been fully understood. Considering the clinical features of IMQ-related dermatitis similar to pseudo-allergic reaction and the presence of large numbers of mast cell in tissues treated with IMQ, the possibility that IMQ-related dermatitis mediated by mast cell-specific Mas-related G protein-coupled receptor X2 (MRGPRX2) should be addressed. To investigate the role of MRGPRX2 in vivo, MrgprB2, the mice homology of human MRGPRX2, was detected in IMQ-induced dermatitis mouse model. Histopathological changes including mast cell degranulation and footpad swelling were assayed in wild-type and MrgprB2-/- mice. The results showed that IMQ application induced dermatitis and footpad swelling with inflammatory cells infiltration plus mast cell activation in the skin of wild-type mice but reduced significantly in MrgprB2-/- mice. Further, compared to wild-type mice, serum histamine and inflammatory cytokine levels were compromised in MrgprB2-/- mice treated with IMQ, while the serum IgE level didn't change significantly. In vitro studies, levels of mediators released from murine peritoneal mast cells (MPMCs) after IMQ treatment were increased in a dose-dependent manner, which were much mild in MPMCs from MrgprB2-/- mice. Intracellular Ca2+ concentration was increased in a dose dependent manner after IMQ treatment both in MrgprB2-HEK293 and MRGPRX2-HEK293 cells. Moreover, β-hexosaminidase released after IMQ treatment was blocked by siRNA directed at the MRGPRX2 receptor in LAD2 cells. In summary, MrgprB2 /MRGPRX2 mediate mast cell activation and participate in IMQ-related dermatitis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect