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Published on: April 16, 2019
Der p2 activates airway smooth muscle cells in a TLR2/MyD88-dependent manner to induce an inflammatory response
Ya-Ling Chiou1, Ching-Yuang Lin
1Institute of Immunology & Microbiology, National Yang-Ming University, Taipei, Taiwan, ROC.
Abstract:
Der p2 is a major allergen from Dermatophagoides pteronyssinus, the main species of house dust mite and a major inducer of asthma, inducing harmful respiratory inflammatory responses by activating cells in the respiratory tract, leading to an unstable status. We hypothesize that Der p2 may induce local inflammatory responses by directly affecting airway smooth muscle (ASM) cells. In this study, we demonstrated that Der p2 raised nuclear factor-kappa B (NF-kappaB) and extracellular signal-regulated kinase (ERK) 1/2 activation and induced a high level of proinflammatory cytokines expression in primary cultured ASM cells. Der p2 activated the MyD88 signaling pathway through toll-like receptor (TLR) 2, not through TLR4. Notably, Der p2 stimulated ASM cells to increase phosphorylation of ERK1/2 and expression of c-Fos, which were also important in the T helper type 2 (Th2) immune response. These results suggest that Der p2 induces asthma through the MyD88 signaling pathway in respiratory tissue.
Insights
House dust mite allergen Der p2 triggers asthma by activating airway smooth muscle cells. This involves the MyD88 signaling pathway, leading to inflammation and T helper type 2 immune responses.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- Dermatophagoides pteronyssinus (house dust mite) is a primary cause of asthma.
- Der p2, a major allergen from this mite, induces respiratory inflammation.
- The direct impact of Der p2 on airway smooth muscle (ASM) cells requires further elucidation.
Purpose of the Study:
- To investigate the role of Der p2 in activating ASM cells.
- To identify the signaling pathways involved in Der p2-induced ASM cell responses.
- To explore the connection between Der p2, ASM cells, and the T helper type 2 (Th2) immune response in asthma.
Main Methods:
- Primary cultured ASM cells were treated with Der p2.
- Activation of nuclear factor-kappa B (NF-kappaB) and extracellular signal-regulated kinase (ERK) 1/2 was measured.
- Expression of proinflammatory cytokines and c-Fos was assessed.
- The involvement of toll-like receptor (TLR) 2, TLR4, and the MyD88 signaling pathway was investigated.
Main Results:
- Der p2 significantly increased NF-kappaB and ERK1/2 activation in ASM cells.
- Proinflammatory cytokine expression was elevated following Der p2 exposure.
- Der p2 activated the MyD88 pathway via TLR2, but not TLR4.
- Der p2 enhanced ERK1/2 phosphorylation and c-Fos expression, linked to Th2 immunity.
Conclusions:
- Der p2 directly activates ASM cells, contributing to asthma pathogenesis.
- The MyD88 signaling pathway, mediated by TLR2, is crucial for Der p2's effects on ASM cells.
- Der p2-induced ASM cell activation and associated signaling pathways play a role in the Th2 immune response in asthma.
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