The Intervention of CRAC Channels Alleviates Inflammatory Responses in Nasal Polyps

Lin, Lin; Dai, Fei; Chen, Zhongchun; Li-hui, Cai

doi:10.1159/000441109

Cited by 2 publications

(3 citation statements)

References 29 publications

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“…29,30 These processes are pivotal events in the mechanisms of AR. Therefore, based on previous studies, [31][32][33][34][35][36] we hypothesized that there might be expression of Orai1 in nuocytes, and the intervention of this protein might work in the attenuation of allergic reactions.…”

Section: Discussionmentioning

confidence: 99%

Intervention of Orai1 Influences the Response of Nuocytes From Allergic Rhinitis Mice to IL-33

Lin

Wei

Chen

et al. 2019

Ann Otol Rhinol Laryngol

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Objective: Nuocytes are essential in innate type-2 immunity and contribute to the exacerbation of allergic rhinitis (AR). This study aimed to evaluate the intervention of Orai1 on the response of nuocytes from AR mice to interleukin (IL)-33. Methods: We established a murine model of AR. Nuocytes were obtained from the mouse nasal-associated lymphoid tissue. Then, we assessed expressions of Orai1, Ca2+ mean fluorescence intensity (MFI) in nuocytes, and their cellular response to mouse recombinant (rm) IL-33. After that, we administered rmlentivirus vectors (lenti) that encoded small hairpin RNA (shRNA) against ORAI1 (lenti-ORAI1) into nuocytes cultures and again evaluated Orai1 and Ca2+ MFI in nuocytes and their response to rmIL-33. Finally, we adoptively transferred nuocytes alone or nuocytes transfected by lenti or lenti-ORAI1 to AR models to investigate their roles during allergic inflammation. Results: We showed that Orai1 and Ca2+ MFI were upregulated in AR mice nuocytes. These cells were induced to produce more IL-5 and IL-13 by rmIL-33. However, the intervention of Orai1 by lenti-ORAI1 in nuocytes decreased Orai1 and Ca2+ MFI and reduced productions of aforementioned cytokines even after the administration of rmIL-33. Numbers of sneezing, nasal rubbing, and counts of eosinophils were all enhanced after the adoptive transfer of nuocytes. Concentrations of IL-5, IL-13, and IL-33 in the nasal lavage fluid (NLF) of allergic mice were also increased. However, the adoptive transfer of nuocytes transfected by lenti-ORAI1 decreased aforementioned parameters. Conclusion: These findings show that the intervention of Orai1 in nuocytes influences the response of nuocytes to rmIL-33.

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Section: Discussionmentioning

confidence: 99%

Intervention of Orai1 Influences the Response of Nuocytes From Allergic Rhinitis Mice to IL-33

Lin

Wei

Chen

et al. 2019

Ann Otol Rhinol Laryngol

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“…Current advancements in the understanding of CRSwNP pathogenesis are focused on the roles of nasal epithelial cells [19]. Epithelial barrier dysfunction plays crucial roles in the formation and development of NP with elevated inflammatory mediators [19].…”

Section: Introductionmentioning

confidence: 99%

“…Epithelial barrier dysfunction plays crucial roles in the formation and development of NP with elevated inflammatory mediators [19]. An elegant study demonstrates that bronchial epithelial cells can produce 5-oxo-ETE under the condition of oxidative stress, which may contribute to eosinophil infiltration in allergic diseases [20].…”

Section: Introductionmentioning

confidence: 99%

5-Oxo-ETE from Nasal Epithelial Cells Upregulates Eosinophil Cation Protein by Eosinophils in Nasal Polyps in vitro

Lin¹,

Chen²,

Tang³

et al. 2018

Int Arch Allergy Immunol

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Background: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a potent eosinophil chemoattractant and activator that is synthesized not only in inflammatory cells but also in bronchial epithelial cells. The purpose of this study is to clarify whether 5-oxo-ETE can promote the production of eosinophil cation protein (ECP) by eosinophils in nasal polyps (NP) in vitro, and whether normal nasal epithelial cells can produce this lipid mediator in response to oxidative stress. Materials and Methods: Nasal biopsy samples were obtained from normal subjects or subjects with chronic rhinosinusitis with NP. The infiltration of eosinophil in NP was detected and cultured. After that, concentrations of ECP in eosinophil and NP cultures were evaluated after the treatment of 5-oxo-ETE or 5-oxo-ETE + its receptor (OXER) antagonist, pertussis toxin (PT). Then we studied the synthesis of 5-oxo-ETE after H₂O₂ stimulation by normal nasal epithelial cells and by epithelial cells of NP alone in the cultures, and also determined the OXER expression in NP. Results: The number of infiltrative eosinophils in NP was increased. The ECP levels in eosinophil and NP cultures were enhanced after the administration of 5-oxo-ETE, and decreased by the PT treatment. 5-Oxo-ETE was upregulated in the cultures of nasal epithelial cells in the presence of H₂O₂ and of NP epithelial cells alone. The OXER was expressed in inflammatory cells, and not in epithelial cells. Conclusion: 5-Oxo-ETE produced by nasal epithelial cells may play a role in the formation and development of NP.

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The Intervention of CRAC Channels Alleviates Inflammatory Responses in Nasal Polyps

Cited by 2 publications

References 29 publications

Intervention of Orai1 Influences the Response of Nuocytes From Allergic Rhinitis Mice to IL-33

Intervention of Orai1 Influences the Response of Nuocytes From Allergic Rhinitis Mice to IL-33

5-Oxo-ETE from Nasal Epithelial Cells Upregulates Eosinophil Cation Protein by Eosinophils in Nasal Polyps in vitro

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