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

Abstract

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 µg/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 downregulated 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.

• Authors: Wei Wu, Chun-Xia Wang, Hui Chen, Jing Zhou, Jin-Zhao Zhang, Lin Gao, Hong-Yan Zhou
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 4 Pg. 5307-13 (Oct 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 26238189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Dermatophagoides
• B7-1 Antigen
• B7-2 Antigen
• Cytokines
• RNA, Small Interfering
• Toll-Like Receptor 2
• Proto-Oncogene Proteins c-kit

Topics

• Animals
• Antigens, Dermatophagoides (immunology)
• B7-1 Antigen (genetics, metabolism)
• B7-2 Antigen (genetics, metabolism)
• Cytokines (metabolism)
• Dendritic Cells (immunology, metabolism)
• Down-Regulation
• Gene Expression
• Gene Expression Regulation
• Male
• Mice
• Proto-Oncogene Proteins c-kit (genetics, metabolism)
• Pyroglyphidae (immunology)
• RNA Interference
• RNA, Small Interfering (genetics)
• Toll-Like Receptor 2 (genetics, metabolism)