House dust mite allergens mediate the activation of c-kit in dendritic cells via Toll-like receptor 2

作者:Wu, Wei*; Wang, Chun-Xia; Chen, Hui; Zhou, Jing; Zhang, Jin-Zhao; Gao, Lin; Zhou, Hong-Yan
来源:Molecular Medicine Reports, 2015, 12(4): 5307-5313.
DOI:10.3892/mmr.2015.4092

摘要

Several studies have demonstrated that the c-kit proto-oncogene and its ligand, stem cell factor, are important in the development of asthma. House dust mite (HDM; Dermatophagoides pteronyssinus) allergens are a major trigger in the development and exacerbation of asthma. HDM allergens can induce the activation of c-kit in dendritic cells (DCs), leading to the development of allergic asthma. Previous studies have demonstrated that activation of Toll-like receptor 2 (TLR2) evokes a T helper (Th)2 immune response and promotes experimental asthma. The aim of the present study was to assess whether HDM mediates the activation of c-kit in DCs via TLR2. Monocyte-derived DCs were generated from C57BL/6 mice, and cultured with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. The DCs were then sensitized with HDM (10 mu g/ml) for 72 h. TLR2-specific small interfering (si)RNA was used to silence and inhibit the expression of TLR2 in the DCs. The expression levels of c-kit and B7 (CD80/CD86) were measured, by analyzing the DC culture supernatant for the presence of IL-6 and IL-12. Inhibition of TLR2 using specific siRNA down-regulated the expression of c-kit in the HDM-activated DCs. In addition, silencing of TLR2 inhibited the expression of CD80/CD86, decreased the production of IL-6, and increased the production of IL-12. These results indicated that TRL2 are important in the activation of c-kit by HDM in DCs.