Sun X. · Xu Y. · Zhou J.

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Department of Otorhinostomology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China

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Article / Publication Details

First-Page Preview

Received: July 20, 2022
Accepted: December 03, 2022
Published online: February 01, 2023

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 1

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

Introduction: DPP4 is thought to be involved in certain immune processes and plays an important role in allergic reactions in the lungs. The effect of the DPP4 inhibitor sitagliptin on the effector phase of allergic rhinitis (AR) in ovalbumin (OVA)-sensitized mice and on mast cell degranulation in vitro was assessed. Methods: The AR mouse model was established by intraperitoneal injection combined with OVA intranasal method. OVA was injected intraperitoneally 3 times for the first 2 weeks, and the mice were subsequently given DPP4 inhibitors by oral gavage, accompanied by an OVA intranasal challenge. The impacts of DPP4 inhibitors on DPP4 levels in mouse model were determined. Nasal mucosa tissue was collected for H&E staining and toluidine blue staining. Immunoglobulin E (IgE) levels and histamine levels were analyzed, and IL-4, IL-5, and IL-12 as well as IFN-γ levels were assessed. Following the treatment of dinitrophenol (DNP)-IgE or DNP-IgE plus sitagliptin in RBL-2H3 cells, β-hexosaminidase activity was analyzed and toluidine blue staining was performed. Results: DPP4 level was reduced in AR patients, as well as in AR mouse models. Nasal allergic symptoms such as sneezing and nose-scratching showed high frequency in OVA-induced mice. Sitagliptin treatment during the intranasal challenge of OVA decreased DPP4 levels, suppressed allergic symptoms, eosinophil infiltration, IgE levels, mast cell infiltration, as well as the levels of inflammatory cytokines. We further found that sitagliptin inhibited mast cell activation and histamine levels in vitro. Conclusion: Sitagliptin suppresses the effector phase of AR, and this mechanism is partly attributed to the suppression of inflammatory response and mast cell degranulation.

© 2023 S. Karger AG, Basel

References Zellweger F, Eggel A. IgE-associated allergic disorders: recent advances in etiology, diagnosis, and treatment. Allergy. 2016;71(12):1652–61. Bousquet J, Schünemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, et al. Allergic rhinitis and its impact on asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol. 2012;130(5):1049–62. Nargis T, Chakrabarti P. Significance of circulatory DPP4 activity in metabolic diseases. IUBMB life. 2018;70(2):112–9. Nader MA. Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma. Int Immunopharmacol. 2015;29(2):761–9. Klemann C, Wagner L, Stephan M, von Hörsten S. Cut to the chase: a review of CD26/dipeptidyl peptidase-4’s (DPP4) entanglement in the immune system. Clin Exp Immunol. 2016;185(1):1–21. Chen HH, Li SY, Chen W, Kao CH. Association between dipeptidyl peptidase-4 inhibitors and allergic rhinitis in asian patients with diabetes. Int J Environ Res Public Health. 2019;16(8):1323. Xue K, Yang J, Zhao Y, Cheng J, Wang Z. Identification of susceptibility genes to allergic rhinitis by gene expression data sets. Clin Transl Sci. 2020;13(1):169–78. Shao S, Xu Q, Yu X, Pan R, Chen Y. Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions. Pharmacol Ther. 2020;209:107503. Subspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck SurgerySubspecialty Group of Rhinology, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of allergic rhinitis]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;51(1):6–24. Fan Y, Yang C, Zhou J, Cheng X, Dong Y, Wang Q, et al. Regulatory effect of glutathione on treg/Th17 cell balance in allergic rhinitis patients through inhibiting intracellular autophagy. Immunopharmacol Immunotoxicol. 2021;43(1):58–67. Van Nguyen T, Piao CH, Fan YJ, Shin DU, Kim SY, Song HJ, et al. Anti-allergic rhinitis activity of α-lipoic acid via balancing Th17/Treg expression and enhancing Nrf2/HO-1 pathway signaling. Sci Rep. 2020;10(1):12528. Jin C, Ye K, Luan H, Liu L, Zhang R, Yang S, et al. Tussilagone inhibits allergic responses in OVA-induced allergic rhinitis Guinea pigs and IgE-stimulated RBL-2H3 cells. Fitoterapia. 2020;144:104496. He Y, Yang G, Yao F, Xian Y, Wang G, Chen L, et al. Sitagliptin inhibits vascular inflammation via the SIRT6-dependent signaling pathway. Int Immunopharmacol. 2019;75:105805. Fu S, Ni S, Wang D, Hong T. Coptisine suppresses mast cell degranulation and ovalbumin-induced allergic rhinitis. Molecules. 2018;23(11):3039. Shao YY, Zhou YM, Hu M, Li JZ, Chen CJ, Wang YJ, et al. The anti-allergic rhinitis effect of traditional Chinese medicine of shenqi by regulating mast cell degranulation and Th1/Th2 cytokine balance. Molecules. 2017;22(3):504. Hoyte FCL, Nelson HS. Recent advances in allergic rhinitis. F1000Research. 2018.7. Bernstein DI, Schwartz G, Bernstein JA. Allergic rhinitis: mechanisms and treatment. Immunol Allergy Clin North Am. 2016;36(2):261–78. Zhang S, Dong D, Zhang Y, Wang J, Liu L, Zhao Y. miR-124-3p relieves allergic rhinitis by inhibiting dipeptidyl peptidase-4. Int Immunopharmacol. 2021;101(Pt B):108279. Wu TF, Chan YY, Shi WY, Jhong MT. Uncovering the molecular mechanism of anti-allergic activity of silkworm pupa-grown cordyceps militaris fruit body. Am J Chin Med. 2017;45(3):497–513. Cardamone C, Parente R, Feo GD, Triggiani M. Mast cells as effector cells of innate immunity and regulators of adaptive immunity. Immunol Lett. 2016;178:10–4. Pope SM, Zimmermann N, Stringer KF, Karow ML, Rothenberg ME. The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. J Immunol. 2005;175(8):5341–50. Article / Publication Details

First-Page Preview

Received: July 20, 2022
Accepted: December 03, 2022
Published online: February 01, 2023

Number of Print Pages: 10
Number of Figures: 6
Number of Tables: 1

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

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