Knockdown of DDX3Y alleviates ovalbumin-induced allergic rhinitis in mice by regulating NF-κB pathway

Main Article Content

Ying Xu
Xiaofeng Gu
Jian Wu
Wenmin Lu

Keywords

allergic rhinitis, DDX3Y, inflammation, NF-κB pathway, ovalbumin-induced model

Abstract

Allergic rhinitis (AR), a type of chronic inflammatory disease that exists in the nasal mucosa, significantly impacts the quality of life. DDX3Y gene encodes an RNA helicase belonging to the DEAD-box protein family and is part of the DDX3 subfamily that affects the progression of multiple diseases. However, the specific role and mechanisms of DDX3Y in AR remain unclear. This study investigates the effects of DDX3Y knockdown on ovalbumin (OVA)-induced AR in mice. We found that DDX3Y is highly expressed in the nasal mucosa of AR mice. Knockdown of DDX3Y in OVA-induced AR mice significantly alleviated nasal manifestations, reduced immunoglobulin E and histamine levels, and improved nasal mucosal histopathology. Additionally, knockdown of DDX3Y suppressed secretion of inflammatory factor nuclear factor kappa B (NF-κB) phosphorylation, thereby mitigating local inflammatory responses. These findings suggested that targeting DDX3Y could offer a novel therapeutic strategy for managing AR by modulating the NF-κB pathway.

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References

1 Yang Y, Wang L, Wang S, Wang Y, Du Y, Fan Y. Luteolin restored Treg/Th17 balance to ameliorate allergic rhinitis in a mouse model. Immunopharmacol Immunotoxicol. 2023;45(4):461–8. 10.1080/08923973.2023.2166527

2 Pfaar O, Gehrt F, Li H, Rudhart SA, Nastev A, Stuck BA, et al. Anti-IgE: A treatment option in allergic rhinitis? Allergol Select. 2021;5:119–27. 10.5414/ALX02205E

3 Ryu G, Bae JS, Kim JH, Kim EH, Chung YJ, Mo JH. Sneezing and rubbing counts in allergic rhinitis mouse models are a reliable indicator of type 2 immune response. Clin Exp Otorhinolaryngol. 2020;13(3):308–11. 10.21053/ceo.2019.02005

4 Park SY, Lee YY, Kim MH, Kim CE. Deciphering the systemic impact of herbal medicines on allergic rhinitis: A network pharmacological approach. Life (Basel). 2024;14(5):553. 10.3390/life14050553

5 Hu L, He W, Li J, Miao Y, Liang H, Li Y. The role of adenoid immune phenotype in polysensitized children with allergic rhinitis and adenoid hypertrophy. Pediatr Allergy Immunol. 2024;35(6):e14166. 10.1111/pai.14166

6 Li HT, Chen ZG, Lin YS, Liu H, Ye J, Zou XL, et al. CpG-ODNs and budesonide act synergistically to improve allergic responses in combined allergic rhinitis and asthma syndrome induced by chronic exposure to ovalbumin by modulating the TSLP-DC-OX40L axis. Inflammation. 2018;41(4):1304–20. 10.1007/s10753-018-0779-6

7 Dai L, Liu B, Lin J, Jiang Y, Li Y, Yao Z, et al. Long-acting anti-inflammatory injectable DEX-gel with sustained release and self-healing properties regulates T(H)1/T(H)2 immune balance for minimally invasive treatment of allergic rhinitis. J Nanobiotechnol. 2024;22(1):51. 10.1186/s12951-024-02306-w

8 Gong C, Krupka JA, Gao J, Grigoropoulos NF, Giotopoulos G, Asby R, et al. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. Mol Cell. 2021;81(19):4059–75 e11. 10.1016/j.molcel.2021.07.041

9 Jia R, Zhao XF. MicroRNA-497 functions as an inflammatory suppressor via targeting DDX3Y and modulating toll-like receptor 4/NF-kappaB in cigarette smoke extract-stimulated human bronchial epithelial cells. J Gene Med. 2020;22(1):e3137. 10.1002/jgm.3137

10 Hoch D, Novakovic B, Cvitic S, Saffery R, Desoye G, Majali-Martinez A. Sex matters: XIST and DDX3Y gene expression as a tool to determine fetal sex in human first trimester placenta. Placenta. 2020;97:68–70. 10.1016/j.placenta.2020.06.016

11 Fan C, Wang W, Yu Z, Wang J, Xu W, Ji Z, et al. M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-kappaB signaling axis. J Nanobiotechnol. 2024;22(1):301. 10.1186/s12951-024-02556-8

12 Reza A, Mesgin RM, Nazari-Khanamiri F, Abdyazdani N, Imani Z, Talatapeh SP, et al. Mesenchymal stem cells-derived exosomes: novel carriers for nanoparticle to combat cancer. Eur J Med Res. 2023 Dec 9;28(1):579. 10.1186/s40001-023-01556-y

13 Wei Z, Yu H, Zhao H, Wei M, Xing H, Pei J, et al. Broadening horizons: Ferroptosis as a new target for traumatic brain injury. Burns Trauma. 2024;12:tkad051. 10.1093/burnst/tkad051

14 Zhang FZ, Tan M, Zeng J, Qi XW, Zhang YT, Che YT, et al. A supramolecular assembly of EGCG for long-term treatment of allergic rhinitis. ACS Biomater Sci Eng. 2024;10(4):2282–98. 10.1039/D3BM02122J10.1021/acsbiomaterials.4c00091

15 Zhan J, Qi Y, Fu Y, Zheng J, Wu J, Wei X, et al. LncRNA ZFAS1 alleviated NLRP3 inflammasome-mediated pyroptosis through regulating miR-96-5p/Smad7 signaling in allergic rhinitis. Int Arch Allergy Immunol. 2024;185(7):704–717. 10.1159/000535646

16 Huyin Yang DL, Yanping W. Physalin A exerts neuroprotective effects: Inhibition of OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells. Signa Vitae. 2023;19(6):168–74.

17 Zheng Z, Wang P. Serum ATG5 concentration relates to Th2 cell, nasal symptoms and therapeutic outcomes in allergic rhinitis patients. Biomark Med. 2023;17(8):437–44. 10.2217/bmm-2023-0152

18 Hu X, Liu S, Jing Z, He Y, Qin G, Jiang L. Immunomodulation in allergic rhinitis: Insights from Th2 cells and NLRP3/IL-18 pathway. Cell Biochem Funct. 2024;42(3):e3997. 10.1002/cbf.3997

19 Vogt PH, Rauschendorf MA, Zimmer J, Drummer C, Behr R. AZFa Y gene, DDX3Y, evolved novel testis transcript variants in primates with proximal 3 UTR polyadenylation for germ cell specific translation. Sci Rep. 2022;12(1):8954. 10.1038/s41598-022-12474-0

20 Qiao Y, Chen J. Investigating the inflammatory cascade effect of basophil activation in children with allergic rhinitis or asthma via the IgE–FcεRI–NF-κB signaling pathway. Adv Clin Exp Med. 2021;30(7):673–9. 10.17219/acem/135756

21 Fan Y, Nguyen TV, Piao CH, Shin HS, Song CH, Chai OH. Fructus Amomi extract attenuates nasal inflammation by restoring Th1/Th2 balance and down-regulation of NF-kappaB phosphorylation in OVA-induced allergic rhinitis. Biosci Rep. 2022;42(3):BSR20212681. 10.1042/BSR20212681