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Budesonide suppresses nasal mucosal remodeling by regulating IL-4/IL-13/STAT6 pathway in rats with allergic rhinitis



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Budesonide suppresses nasal mucosal remodeling by regulating IL-4/IL-13/STAT6 pathway in rats with allergic rhinitis


budesonide; allergic rhinitis; interleukin-4; interleukin-13; STAT6; liquid chip; rats


ObjectiveTo investigate the effect of budesonide on nasal mucosal remodeling and the role of IL4/IL13/STAT6 signaling pathway in mediating this effect in rats with allergic rhinitis (AR). MethodsA total of 102 rats were randomly allocated into 3 equal groups, namely ARPBS group, ARbudesonide group and blank group. The rats in ARPBS and ARbudesonide groups were sensitized by challenges with ovalbumin to establish models of AR, and were subsequently treated by daily intranasal instillation with PBS and budesonide with aid of Eppendof for 7 consecutive days, respectively. The rats in the blank group were not challenged with ovalbumin and were treated with PBS in the same manner. Animal Assessment Scale was used to assess the behavioral changes of the rats after the treatments. Enzymelinked immunosorbent assay (ELISA) was used to detect the serum levels of histamine (His) and IgE, and the levels of interleukin (IL)13 and IL4 in the serum and bronchoalveolar lavage were analyzed with a Luminex liquid chip. STAT6 mRNA expression in the nasal mucosal was assessed with qPCR, and the protein expression levels of STAT6 and PSTAT6 were tested with Western blotting. HE staining and transmission electron microscopy were used to assess nasal septum remodeling after the treatments. ResultsThe rat models of AR all had a behavioral assessment score over 5 by the Animal Assessment Scale. Compared with those in the blank group, the rats with AR showed significantly increased serum levels of His and IgE, increased levels of IL13 and IL4 in both the serum and bronchoalveolar lavage, and also increased expression of STAT6 and PSTAT6 in the nasal mucosa (P<0.01). Budesonide treatment of the rats with AR for 7 days obviously lowered the serum levels of His and IgE, which remained unchanged in rats with PBS treatment. Compared with PBS treatment, budesonide treatment also decreased the levels of IL4 and IL13 in the serum and bronchoalveolar lavage and downregulated the expression of STAT6 and PSTAT6 in the nasal mucosa (P<0.01). HE staining and transmission electron microscopy showed that budesonide treatment partially reversed ARinduced reduction of nasal cilia in the rats without causing obvious changes in cell connection. ConclusionBudesonide improves the pathologies in the nasal mucosa of rats with AR by inhibiting IL4, IL13, and pSTAT6.


[1]DYKEWICZ M S, WALLACE D V, BAROODY F, et al. Treatment of seasonal allergic rhinitis: an evidencebased focused 2017 guideline update[J]. Ann Allergy Asthma Immunol, 2017,119(6): 489-511.e41. DOI: 10.1016/j.anai. 2017.08.012.
[2]RANGAMUWA K B, YOUNG A C, THIEN F. An epidemic of thunderstorm asthma in melbourne 2016: asthma, rhinitis, and other previous allergies[J]. Asia Pac Allergy, 2017,7(4): 193-198. DOI: 10.5415/apallergy.2017.7.4.193.
[3]YU S, HAN B, LIU S, et al. Derp1modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis[J]. Mol Immunol, 2017, 90: 172-181. DOI: 10.1016/j.molimm.2017. 07.015.
[4]MAY J R, DOLEN W K. Management of allergic rhinitis: a review for the community pharmacist[J]. Clin Ther, 2017, 39(12): 2410-2419. DOI: 10.1016/j.clinthera.2017.10. 006.
[5]LEE H J, KIM B, IM N R, et al. Decreased expression of Ecadherin and ZO1 in the nasal mucosa of patients with allergic rhinitis: altered regulation of Ecadherin by IL4, IL5, and TNFalpha[J]. Am J Rhinol Allergy, 2016, 30(3): 173-178. DOI: 10.2500/ajra.2016.30.4295.
[6]BARIK S, MILLER M M, CATTINROY A N, et al. IL4/IL13 signaling inhibits the potential of early thymic progenitors to commit to the T cell lineage[J]. J Immunol, 2017,199(8): 2767-2776. DOI: 10.4049/jimmunol.1700498.
[7]SUN L, REN X, WANG I C, et al. The FOXM1 inhibitor RCM1 suppresses goblet cell metaplasia and prevents IL13 and STAT6 signaling in allergenexposed mice[J]. Sci Signal, 2017,10(475): eaai8583. DOI: 10.1126/scisignal.aai8583.
[8]HOSOYA K, SATOH T, YAMAMOTO Y, et al. Gene silencing of STAT6 with siRNA ameliorates contact hypersensitivity and allergic rhinitis[J]. Allergy, 2011, 66(1): 124-131. DOI: 10.1111/j.13989995.2010.02440. x.
[9]RICCIO A M, TOSCA M A, COSENTINO C, et al. Cytokine pattern in allergic and nonallergic chronic rhinosinusitis in asthmatic children[J]. Clin Exp Allergy, 2002, 32(3): 422-426. 
[10]GHARIB ALY M A, EL TABBAKH M T, HEISSAM W F, et al. The study of a possible correlation between serum levels of interleukin 17 and clinical severity in patients with allergic rhinitis[J]. Allergy Rhinol (Providence), 2017, 8(3): e126-e131. DOI: 10.2500/ar.2017.8.0207.
[11]PARULEKAR A D, KAO C C, DIAMANT Z, et al. Targeting the interleukin4 and interleukin13 pathways in severe asthma: current knowledge and future needs[J]. Curr Opin Pulm Med, 2018,24(1): 50-55. DOI: 10.1097/MCP. 0000000000000436.
[12] 赵秀杰, 董震, 杨占泉, 等. 鼻超敏反应实验模型的建立[J]. 中华耳鼻咽喉科杂志, 1993, 28(1): 17-18.
ZHAO X J, DONG Z,YANG Z Q, et al. Establishment of experimental model of nasal hypersensitivity[J]. Chin J Otorhinolaryngol Head Neck Surg, 1993, 28(1): 17-18.


Last Update: 2018-07-03