The Intervention of CRAC Channels Alleviates Inflammatory Responses in Nasal Polyps.
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.


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.
Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, PR China.
Lin
L
Lin
Fei
F
Dai
Zhongchun
Z
Chen
Lihui
L
Cai
D000328:Adult; D000368:Aged; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D000071740:ORAI1 Protein; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012220:Rhinitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D012852:Sinusitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D001896:Boron Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018836:Inflammation Mediators; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D012333:RNA, Messenger; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium