山东大学耳鼻喉眼学报 ›› 2026, Vol. 40 ›› Issue (6): 10-21.

• 气道变态反应性疾病：从机制到实践 • 上一篇    

PM2.5有机组分诱导鼻上皮细胞损伤与成纤维细胞炎症表型激活

周嘉瑶1,2,3,朱莹1,2,3,胡慧琳4,李志鹏1,2,3,林海1,2,3,唐如1,2,3,茆松1,2,3,顾月龙1,2,3,赵岳4,张维天1,2,3   

  1. 1.上海交通大学医学院附属第六人民医院 耳鼻咽喉头颈外科, 上海 200233;
    2.上海交通大学 耳鼻咽喉头颈外科研究所, 上海 200233;
    3.上海市睡眠呼吸障碍疾病重点实验室, 上海 200233;
    4.上海交通大学 环境科学与工程学院, 上海 200240
  • 发布日期:2026-11-03
  • 通讯作者: 张维天. E-mail:wtzhang@sjtu.edu.cn
  • 基金资助:
    国家自然科学基金(82271137);上海市重中之重临床医学中心建设项目(2023ZZ02008)

Nasal epithelial cell injury and fibroblast inflammatory phenotype activation induced by PM2.5 organic components

ZHOU Jiayao1,2,3, ZHU Ying1,2,3, HU Huilin4, LI Zhipeng1,2,3, LIN Hai1,2,3, TANG Ru1,2,3, MAO Song1,2,3, GU Yuelong1,2,3, ZHAO Yue4, ZHANG Weitian1,2,3   

  1. 1. Department of Otorhinolaryngology & Head and Neck Surgery , Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China2. Institute of Otorhinolaryngology Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai 200233, China3. Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai 200233, China4. School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
  • Published:2026-11-03

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摘要： 目的 旨在探究细颗粒物(fine particulate matter,PM2.5)中有机组分(organic compounds, OCs)对人鼻上皮细胞(human nasal epithelial cells, hNEs)与成纤维细胞(human nasal fibroblasts, hNFs)的效应差异及机制。 方法 采集PM2.5样本并萃取其中的OCs,刺激体外分离培养的原代hNEs和hNFs。采用细胞计数试剂盒-8(cell counting kit-8, CCK-8)和乳酸脱氢酶(lactate dehydrogenase, LDH)方法检测细胞活力与毒性;采用转录组测序和生物信息学方法分析差异表达基因、功能富集和蛋白互作网络分析;采用RT-qPCR验证测序结果。 结果 OCs以浓度和时间依赖性抑制hNEs增殖并诱导细胞毒性,但对hNFs活力无影响。OCs刺激后,hNEs中CYP1A1、CYP1B1表达上调、AHRR下调,同时MT1家族基因表达上调。而在hNFs中,OCs刺激上调炎症因子LIF、IL6及其受体IL6R的表达,且AHRR代偿性升高。 结论 OCs通过差异性调控AHRR诱导hNEs损伤与hNFs炎症表型激活,二者协同参与慢性鼻窦炎的炎症和组织重塑。

关键词: 细颗粒物, 有机组分, 鼻上皮细胞, 鼻成纤维细胞, 慢性鼻窦炎

Abstract: Objective The present study was conducted with the objective of investigating the differential effects of organic compounds(OCs)within PM2.5 on human nasal epithelial cells(hNEs)and human nasal fibroblasts(hNFs), and elucidating the underlying molecular mechanisms. Methods PM2.5 samples were collected in Shanghai, and OCs were extracted using dichloromethane. Primary hNEs and hNFs were isolated in vitro and stimulated with different concentrations of OCs. The assessment of cell viability and toxicity wasconducted by means of thecell counting kit-8(CCK-8)and lactate dehydrogenase(LDH)assays. The employment of transcriptomic sequencing(RNA-seq)and bioinformatics analysis was undertaken for the identification of differentially expressed genes, the performance of functional enrichment analysis, and the construction of protein-protein interaction networks. The validation of the sequencing results was conducted through the utilisation of quantitative real-time PCR(RT-qPCR). Results The study demonstrated that OCs significantly inhibited the proliferation of hNEs and induced cytotoxicity in a concentration- and time-dependent manner. However, no effect was observed on the viability of hNFs. Subsequent to OC stimulation, the expression levels of CYP1A1 and CYP1B1 were observed to be elevated, while AHRR expression was reduced in hNEs. Concurrently, the expression of MT1 family genes was found to be upregulated, suggesting activation of the AHR-CYP pathway and oxidative stress damage. Conversely, in hNFs, OC stimulation led to an upregulation of inflammatory factors LIF, IL6, and its receptor IL6R, accompanied by a compensatory increase in AHRR expression. Conclusion The induction of hNEs injury and inflammatory phenotype of hNFs by OCs is attributable to differential regulation of AHRR. These two cell types have been shown to synergistically participate in the inflammatory and remodeling processes of chronic rhinosinusitis, thus providing a novel perspective on the pathogenesis of PM2.5-induced CRS.

Key words: Fine particulate matter, Organic components, Nasal epithelial cells, Nasal fibroblasts, Chronic rhinosinusitis

中图分类号: 

  • R765
[1] Losacco C, Perillo A. Particulate matter air pollution and respiratory impact on humans and animals[J]. Environ Sci Pollut Res Int, 2018, 25(34): 33901-33910. DOI:10.1007/s11356-018-3344-9
[2] Kim B E, Hui-Beckman J W, Nevid M Z, et al. Air pollutants contribute to epithelial barrier dysfunction and allergic diseases[J]. Ann Allergy Asthma Immunol, 2024, 132(4): 433-439. DOI:10.1016/j.anai.2023.11.014
[3] Zhang Z Q, Li J Y, Guo Q, et al. Association between air pollution and allergic upper respiratory diseases: a meta-analysis[J]. Eur Respir Rev, 2025, 34(176): 240266. DOI:10.1183/16000617.0266-2024
[4] Chowdhury P H, Kitamura G, Honda A, et al. Synergistic effect of carbon nuclei and polyaromatic hydrocarbons on respiratory and immune responses[J]. Environ Toxicol, 2017, 32(9): 2172-2181. DOI:10.1002/tox.22430
[5] Cui W, Gao H X, Zhu L R, et al. Short-term association between ambient air pollution and childhood non-allergic rhinitis: a time-series study at a National Children's Regional Medical Center, in Hefei, China, from 2015 to 2021[J]. Ecotoxicol Environ Saf, 2025, 290: 117590. DOI:10.1016/j.ecoenv.2024.117590
[6] Brinchmann B C, Skuland T, Rambøl M H, et al. Lipophilic components of diesel exhaust particles induce pro-inflammatory responses in human endothelial cells through AhR dependent pathway(s)[J]. Part Fibre Toxicol, 2018, 15(1): 21. DOI:10.1186/s12989-018-0257-1
[7] Meng Z Q, Zhang Q X. Damage effects of dust storm PM2.5 on DNA in alveolar macrophages and lung cells of rats[J]. Food Chem Toxicol, 2007, 45(8): 1368-1374. DOI:10.1016/j.fct.2007.01.014
[8] Liu Y, Hu G, Li Y T, et al. Research on the biological mechanism and potential application of CEMIP[J]. Front Immunol, 2023, 14: 1222425. DOI:10.3389/fimmu.2023.1222425
[9] Déciga-Alcaraz A, Tlazolteotl Gómez de León C, Morales Montor J, et al. Effects of solvent extracted organic matter from outdoor air pollution on human type II pneumocytes: Molecular and proteomic analysis[J]. Environ Pollut, 2023, 337: 122551. DOI:10.1016/j.envpol.2023.122551
[10] Kim B E, Hui-Beckman J W, Nevid M Z, et al. Air pollutants contribute to epithelial barrier dysfunction and allergic diseases[J]. Ann Allergy Asthma Immunol, 2024, 132(4): 433-439. DOI:10.1016/j.anai.2023.11.014
[11] Brzezinski M, Martin L, Simpson K, et al. Photodegradation enhances the toxic effect of anthracene on skin[J]. J Hazard Mater, 2024, 471: 134386. DOI:10.1016/j.jhazmat.2024.134386
[12] Hong Z C, Guo Z Q, Zhang R X, et al. Airborne fine particulate matter induces oxidative stress and inflammation in human nasal epithelial cells[J]. Tohoku J Exp Med, 2016, 239(2): 117-125. DOI:10.1620/tjem.239.117
[13] Gu W J, Hou T H, Zhou H W, et al. Ferroptosis is involved in PM2.5-induced acute nasal epithelial injury via AMPK-mediated autophagy[J]. Int Immunopharmacol, 2023, 115: 109658. DOI:10.1016/j.intimp.2022.109658
[14] Hong Z C, Zeng P J, Zhuang G S, et al. Toxicological effects of artificial fine particulate matter in rats through induction of oxidative stress and inflammation[J]. Tohoku J Exp Med, 2021, 255(1): 19-25. DOI:10.1620/tjem.255.19
[15] Yuan J S, Liao Z H, Zhu X H, et al. PM2.5 exacerbates nasal epithelial barrier dysfunction in allergic rhinitis by inducing NLRP3-mediated pyroptosis via the AhR/CYP1A1/ROS axis[J]. J Hazard Mater, 2025, 492: 138145. DOI:10.1016/j.jhazmat.2025.138145
[16] Wang Y, Zheng B W, Xiong P H, et al. PM2.5 induced nasal mucosal barrier dysfunction and epithelial-mesenchymal transition to promote chronic rhinosinusitis through IL4I1-AhR signaling pathway[J]. Toxics, 2025, 13(6): 488. DOI:10.3390/toxics13060488
[17] Shin J M, Yang H W, Park J H, et al. Role of nasal fibroblasts in airway remodeling of chronic rhinosinusitis: the modulating functions reexamined[J]. Int J Mol Sci, 2023, 24(4): 4017. DOI:10.3390/ijms24044017
[18] Ball S L, Mann D A, Wilson J A, et al. The role of the fibroblast in inflammatory upper airway conditions[J]. Am J Pathol, 2016, 186(2): 225-233. DOI:10.1016/j.ajpath.2015.09.020
[19] Kim J S, Choi H, Oh J M, et al. Effect of fluticasone propionate on human nasal fibroblasts exposed to urban particulate matter[J]. Auris Nasus Larynx, 2020, 47(3): 415-424. DOI:10.1016/j.anl.2019.11.002
[20] Zhu Y, Zhang S Y, Gu Y L, et al. PM2.5 activates IL-17 signaling pathway in human nasal mucosa-derived fibroblasts[J]. Int Immunopharmacol, 2024, 128: 111484. DOI:10.1016/j.intimp.2024.111484
[21] Lee D C, Choi H, Oh J M, et al. The effect of urban particulate matter on cultured human nasal fibroblasts[J]. Int Forum Allergy Rhinol, 2018, 8(9): 993-1000. DOI:10.1002/alr.22167
[22] Zhao R W, Guo Z Q, Dong W Y, et al. Effects of PM2.5 on mucus secretion and tissue remodeling in a rabbit model of chronic rhinosinusitis[J]. Int Forum Allergy Rhinol, 2018, 8(11): 1349-1355. DOI:10.1002/alr.22182
[23] Fokkens W J, Lund V J, Hopkins C, et al. European position paper on rhinosinusitis and nasal polyps 2020[J]. Rhinology, 2020, 58(Suppl S29): 1-464. DOI:10.4193/Rhin20.600
[24] Zarba Ł, Piszczatowska K, D(·overz)aman K, et al. The relationship between fine particle matter(PM2.5)exposure and upper respiratory tract diseases[J]. J Pers Med, 2024, 14(1): 98. DOI:10.3390/jpm14010098
[25] Liu B Y, Han Y C, Ye Y Y, et al. Atmospheric fine particulate matter(PM2.5)induces pulmonary fibrosis by regulating different cell fates via autophagy[J]. Sci Total Environ, 2024, 923: 171396. DOI:10.1016/j.scitotenv.2024.171396
[26] 中华人民共和国环境保护部. 环境空气质量标准: GB 3095—2012[S]. 北京: 中国环境科学出版社, 2012: 3-4
[27] Chen S F, Zhou Y Q, Chen Y R, et al. Fastp: an ultra-fast all-in-one FASTQ preprocessor[J]. Bioinformatics, 2018, 34(17): i884-i890. DOI:10.1093/bioinformatics/bty560
[28] Kim D, Langmead B, Salzberg S L. HISAT: a fast spliced aligner with low memory requirements[J]. Nat Methods, 2015, 12(4): 357-360. DOI:10.1038/nmeth.3317
[29] Pertea M, Pertea G M, Antonescu C M, et al. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads[J]. Nat Biotechnol, 2015, 33(3): 290-295. DOI:10.1038/nbt.3122
[30] Li B, Dewey C N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome[J]. BMC Bioinformatics, 2011, 12: 323. DOI:10.1186/1471-2105-12-323
[31] Love M I, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2[J]. Genome Biol, 2014, 15(12): 550. DOI:10.1186/s13059-014-0550-8
[32] Rothhammer V, Quintana F J. The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease[J]. Nat Rev Immunol, 2019, 19(3): 184-197. DOI:10.1038/s41577-019-0125-8
[33] Wang Y, Zheng B W, Xiong P H, et al. PM2.5 induced nasal mucosal barrier dysfunction and epithelial-mesenchymal transition to promote chronic rhinosinusitis through IL4I1-AhR signaling pathway[J]. Toxics, 2025, 13(6): 488. DOI:10.3390/toxics13060488
[34] El Rahman El Mais A, D'Anna B, Albinet A, et al. In vitro assessment of aryl hydrocarbon, estrogen, and androgen receptor-mediated activities of secondary organic aerosols formed from the oxidation of polycyclic aromatic hydrocarbons and furans[J]. Environ Res, 2025, 273: 121220. DOI:10.1016/j.envres.2025.121220
[35] Jin H, Lin Z, Pang T, et al. Effects and mechanisms of polycyclic aromatic hydrocarbons in inflammatory skin diseases[J]. Sci Total Environ, 2024, 925:171492. DOI: 10.1016/j.scitotenv.2024.171492
[36] Vogel C F A, Van Winkle L S, Esser C, et al. The aryl hydrocarbon receptor as a target of environmental stressors-Implications for pollution mediated stress and inflammatory responses[J]. Redox Biol, 2020, 34:101530. DOI: 10.1016/j.redox.2020.101530
[37] Rothhammer V, Quintana F J. The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease[J]. Nat Rev Immunol, 2019, 19(3): 184-197. DOI:10.1038/s41577-019-0125-8
[38] Pavi c M, Tur ci c P, & Ljubojevi c M. Forgotten partners and function regulators of inducible metallothioneins[J]. Arh Hig Rada Toksikol, 2019, 70(4): 256-264. DOI:10.2478/aiht-2019-70-3317
[39] Smith A. Links between cell-surface events involving redox-active copper and gene regulation in the hemopexin heme transport system[J]. Antioxid Redox Signal, 2000, 2(2): 157-175. DOI:10.1089/ars.2000.2.2-157
[40] Liu T T, Jiang B, Fu B Q, et al. PM2.5 induces cardiomyoblast senescence via AhR-mediated oxidative stress[J]. Antioxidants, 2024, 13(7): 786. DOI:10.3390/antiox13070786
[41] Dumoutier L, Van Roost E, Ameye G, et al. IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes[J]. Genes Immun, 2000, 1(8): 488-494. DOI:10.1038/sj.gene.6363716
[42] Zou Q Y, Hong S L, Kang H Y, et al. Effect of di-(2-ethylhexyl)phthalate(DEHP)on allergic rhinitis[J]. Sci Rep, 2020, 10(1): 14625. DOI:10.1038/s41598-020-71517-6
[43] Kim J S, Oh J M, Choi H, et al. Activation of the Nrf2/HO-1 pathway by curcumin inhibits oxidative stress in human nasal fibroblasts exposed to urban particulate matter[J]. BMC Complement Med Ther, 2020, 20(1): 101. DOI:10.1186/s12906-020-02886-8
[44] Nie H P, Liu H L, Shi Y, et al. Effects of different concentrations of oil mist particulate matter on pulmonary fibrosis in vivo and in vitro[J]. Toxics, 2022, 10(11): 647. DOI:10.3390/toxics10110647
[45] Xu Z H, Li Z L, Liao Z Y, et al. PM2.5 induced pulmonary fibrosis in vivo and in vitro[J]. Ecotoxicol Environ Saf, 2019, 171: 112-121. DOI:10.1016/j.ecoenv.2018.12.061
[46] Nguyen H N, Noss E H, Mizoguchi F, et al. Autocrine loop involving IL-6 family member LIF, LIF receptor, and STAT4 drives sustained fibroblast production of inflammatory mediators[J]. Immunity, 2017, 46(2): 220-232. DOI:10.1016/j.immuni.2017.01.004
[47] Sakurai S, Shimizu T, Ohto U. The crystal structure of the AhRR-ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription[J]. J Biol Chem, 2017, 292(43): 17609-17616. DOI:10.1074/jbc.M117.812974
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