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The Intervention of CRAC Channels Alleviates Inflammatory Responses in Nasal Polyps
Lin Lin1, Fei Dai, Zhongchun Chen
1Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, PR China.
Background:
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with Th2-dominant inflammation. However, effective treatments for CRSwNP have not yet been found. This study aimed to investigate the expression of Orai1 in nasal polyps (NP) and the influence on them of the intervention of Ca2+ release-activated Ca2+ (CRAC) channels.
Materials And Methods:
Nasal samples were obtained from normal subjects or subjects with CRSwNP. We studied the distribution of Orai1 protein in NP and normal mucosa (normal group) using immunohistochemistry. These tissues in cultures were then maintained in the absence (control group) or presence of 2-aminoethoxydiphenyl borate (2-APB) for 24 h. Orai1 was examined by means of enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). The Ca2+ mean fluorescence intensity (MFI) was evaluated by flow cytometry, and the inflammatory mediators, including interleukin (IL)-4, IL-5, IL-13, Dermatophagoides pteronyssinus-specific IgE, leukotriene C4 and eosinophil cation protein in cultures, were analyzed with ELISA and real-time RT-PCR.
Results:
The expression of Orai1 was localized to the cytoplasmic membrane of inflammatory cells, and upregulated in NP compared to that in the normal group. However, Orai1 protein was decreased in polyp tissues after the 2-APB treatment. The levels of Ca2+ MFI and above inflammatory mediators were also elevated in NP, and reduced after the 2-APB administration compared to those in the control group.
Conclusions:
Orai1 and CRAC channels may play a crucial role in NP formation and development, and the 2-APB intervention of Orai1 protein may alleviate inflammatory responses in NP.
Insights
Orai1 and calcium release-activated calcium (CRAC) channels are upregulated in nasal polyps, contributing to inflammation. Blocking Orai1 with 2-APB may reduce these inflammatory responses in chronic rhinosinusitis with nasal polyps.
Area of Science:
- Immunology
- Cell Biology
- Otorhinolaryngology
Background:
- Chronic rhinosinusitis with nasal polyps (CRSwNP) exhibits Th2-dominant inflammation.
- Current treatments for CRSwNP remain limited.
- Investigating Orai1 and calcium release-activated calcium (CRAC) channels offers potential therapeutic targets.
Purpose of the Study:
- To examine Orai1 expression in nasal polyps (NP).
- To assess the impact of CRAC channel intervention on Orai1 and inflammatory mediators in NP.
Main Methods:
- Immunohistochemistry, ELISA, and RT-PCR were used to analyze Orai1 expression and inflammatory mediators.
- Flow cytometry measured intracellular calcium levels.
- Nasal tissues were treated with 2-aminoethoxydiphenyl borate (2-APB) to inhibit CRAC channels.
Main Results:
- Orai1 was upregulated in NP compared to normal mucosa.
- 2-APB treatment decreased Orai1 protein levels, intracellular calcium, and key inflammatory mediators (IL-4, IL-5, IL-13, IgE, LTC4, ECP).
- These findings suggest Orai1 plays a role in NP inflammation.
Conclusions:
- Orai1 and CRAC channels are implicated in the pathogenesis of nasal polyps.
- Intervention targeting Orai1 with 2-APB may reduce inflammatory responses in CRSwNP.
- Further research into Orai1 modulation could lead to novel CRSwNP treatments.
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