Sage Journals: Discover world-class research

Abstract

Objective

Glucocorticoids are considered the main treatment option for chronic rhinosinusitis with nasal polyps (CRSwNP), but their effect rate ranges from 60.9% to 80%. Novel therapeutic means should be studied. The purpose of this study was to investigate the expression of Orai1 in nasal polyps (NPs) and the influence of intervention of Orai1 on NPs after in vitro treatment of 2-aminoethoxydiphenyl borate (2-APB).

Study Design

Prospective cross-sectional study.

Setting

University hospital.

Subjects and Methods

Nasal biopsy samples were obtained from normal subjects or subjects with CRSwNP. We studied the localization of Orai1 protein in NPs by using immunohistochemistry. Then these tissues in cultures were maintained in the absence or presence of dexamethasone (DEX) or 2-APB. Orai1 was examined by Western blot, enzyme-linked immunosorbent assay (ELISA), and real-time reverse transcription-polymerase chain reaction (RT-PCR). Inflammatory mediators including interleukin (IL)-1β, IL-5, eosinophil cation protein (ECP), leukotriene (LT)C4, interferon (IFN)-γ, and dermatophagoides pteronyssinus (DP)-specific immunoglobulin E (sIgE) as well as mucins (MUCs) including MUC5B and MUC7 in cultures were analyzed with ELISA and real-time RT-PCR.

Results

The expression of Orai1 was localized to cytoplasmic membrane of inflammatory cells and submucosal glandular cells and was upregulated in NPs compared with normal nasal mucosa. Orai1 was decreased in NPs after in vitro treatment of 2-APB but not after DEX intervention. The levels of inflammatory mediators and mucins were reduced more after 2-APB treatment when compared with those after DEX treatment.

Conclusion

Orai1 may play crucial roles in NP formation, and the intervention of Orai1 may inhibit NP development.

Keywords

nasal polyps inflammation Orai1 DEX 2-APB

Get full access to this article

View all access options for this article.

References

Larsen

Tos

. Origin of nasal polyps: an endoscopic autopsy study. Laryngoscope. 2004;114:710-719.

Desrosiers

Evans

Keith

. Canadian clinical practice guidelines for acute and chronic rhinosinusitis. Allergy Asthma Clin Immunol. 2011;7:1-38.

Stoop

van der Heijden

Biewenga

van der Baan

. Eosinophils in nasal polyps and nasal mucosa: an immunohistochemical study. J Allergy Clin Immunol. 1993;91:616-622.

Bachert

Gevaert

van Cauwenberge

. Staphylococcus aureus super antigens and airway disease. Curr Allergy Asthma Rep. 2002;2:252-258.

Necela

Cidlowski

. Mechanisms of glucocorticoid receptor action in noninflammatory and inflammatory cells. Proc Am Thorac Soc. 2004;1:239-246.

Fokkens

Lund

Mullol

. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012;3 p preceding table of contents:1-298.

Berridge

Bootman

Roderick

. Calcium signaling: dynamics, homeostasis and remodeling. Nat Rev Mol Cell Biol. 2003;4:517-529.

Vig

Peinelt

Beck

. CRACM1 is a plasma membrane protein essential for store-operated Ca²⁺ entry. Science. 2006;312:1220-1223.

Feske

Gwack

Prakriya

. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006;441:179-185.

10.

Varnai

Hunyady

Balla

. STIM and Orai: the long-awaited constituents of store-operated calcium entry. Trends Pharmacol Sci. 2009;30:118-128.

11.

Gwack

Feske

Srikanth

Hogan

Rao

. Signalling to transcription: store-operated Ca²⁺ entry and NFAT activation in lymphocytes. Cell Calcium. 2007;42:145-156.

12.

Diehl

Krahl

Rinaldi

Norton

Irvin

Rincón

. Inhibition of NFAT specifically in T cells prevents allergic pulmonary inflammation. J Immunol. 2004;172:3597-3603.

13.

Rao

Luo

Hogan

. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707-747.

14.

Bachert

Van Bruaene

Toskala

. Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis—a GALEN study. Allergy. 2009;64:520-533.

15.

Peinelt

Lis

Beck

Fleig

Penner

. 2-Aminoethoxydiphenyl borate directly facilitates and indirectly inhibits STIM1-dependent gating of CRAC channels. J Physiol. 2008;586:3061-3073.

16.

Prakriya

Lewis

. Potentiation and inhibition of Ca(2+) release-activated Ca(2+) channels by 2-aminoethyldiphenyl borate (2-APB) occurs independently of IP(3) receptors. J Physiol. 2001;536(pt 1):3-19.

17.

Feske

. Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol. 2007;7:690-702.

18.

Lin

Zheng

Zhang

Zhao

. 2-Aminoethoxydiphenyl borate administration into the nostril alleviates murine allergic rhinitis. Am J Otolaryngol. 2011;32:318-328.

19.

Lin

Zhao

Yan

Guo

Liang

. Amelioration of Muc5b mucin hypersecretion is enhanced by IL-33 after 2-APB administration in a murine model of allergic rhinitis. Biotech Histochem. 2014;89:273-286.

20.

Park

Lee

Yang

. Organ culture at the air-liquid interface maintains structural and functional integrities of inflammatory and fibrovascular cells of nasal polyps. Am J Rhinol. 2007;21:402-407.

21.

Lee

Nam

Lee

. Dexamethasone induces apoptosis of nasal polyp-derived tissue cultures through JNK and p38 MAPK activation. Clin Exp Otorhinolaryngol. 2014;7:112-118.

22.

Arcimowicz

Balcerzak

Samoliński

. Nasal polyps is not a homogenous pathology. Pol Merkur Lek. 2005;19:276-279.

23.

Bernstein

Yankaskas

. Increased ion transport in cultured nasal epithelial cells. Arch Otolaryngol Head Neck Surg. 1994;120:993-996.

24.

Takeno

Hirakawa

Ueda

Furukido

Osada

Yajin

. Nuclear factor-kappa B activation in the nasal polyp epithelium: relationship to local cytokine gene expression. Laryngoscope. 2002;112:53-58.

25.

Kato

Schleimer

. Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity. Curr Opin Immunol. 2007;19:711-720.

26.

Bachert

Wagenmann

Hauser

Rudack

. IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol. 1997;99:837-842.

27.

Hamelmann

Gelfand

. IL-5-induced airway eosinophilia—the key to asthma? Immunol Rev. 2001;179:182-191.

28.

Watanabe

Shirasaki

Kanaizumi

Himi

. Effects of glucocorticoids on infiltrating cells and epithelial cells of nasal polyps. Ann Otol Rhinol Laryngol. 2004;113:465-473.

29.

Gleich

. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol. 2000;105:651-663.

30.

Arcimowicz

Balcerzak

Samoliński

. Nasal polyps is not a homogenous pathology. Pol Merkur Lek. 2005;19:276-279.

31.

Perez-Novo

Claeys

Van Cauwenberge

Bachert

. Expression of eicosanoid receptors subtypes and eosinophilic inflammation: implication on chronic rhinosinusitis. Respir Res. 2006;7:75.

32.

Pawankar

. Mast cells in allergic airway disease and chronic rhinosinusitis. Chem Immunol Allergy. 2005;87:111-129.

33.

Abraham

St John

. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. 2010;10:440-452.

34.

Meltzer

Hamilos

Hadley

. Rhinosinusitis: establishing definitions for clinical research and patient care. J Allergy Clin Immunol. 2004;114:155-212.

35.

Zhang

Holtappels

Claeys

Huang

van Cauwenberge

Bachert

. Pattern of inflammation and impact of Staphylococcus aureus enterotoxins in nasal polyps from southern China. Am J Rhinol. 2006;20:445-450.

36.

Kang

Nahm

Suh

Kim

Park

. Local production of specific IgE antibody to house dust mite in nasal polyp tissue. J Asthma Allergy Clin Immunol. 1998;18:426-433.

37.

Tomassini

Tsicopoulos

Tai

. Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation. J Allergy Clin Immunol. 1991;88:365-375.

38.

Suh

Park

Nahm

Kim

Lee

Park

. Role of IgG, IgA, and IgE antibodies in nasal polyp tissue: their relationships with eosinophilic infiltration and degranulation. J Korean Med Sci. 2002;17:375-380.

39.

Gevaert

Nouri-Aria

. Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. Allergy. 2013;68:55-63.

40.

Ali

Wilson

Bennett

Pearson

. Mucin gene expression in nasal polyps. Acta Otolaryngol. 2005;125:618-624.

41.

Sharma

Dudus

Nielsen

. MUC5B and MUC7 are differentially expressed in mucous and serous cells of submucosal glands in human bronchial airways. Am J Respir Cell Mol Biol. 1998;19:30-37.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.25 MB

5.16 MB

5.38 MB

In Vitro Treatment with 2-APB Inhibits the Inflammation in Nasal Polyps

Abstract

Objective

Study Design

Setting

Subjects and Methods

Results

Conclusion

Keywords

Get full access to this article

References

Supplementary Material