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目的 研究布地奈德(BUD)对S100钙结合蛋白A4(S100A4)诱导的肥大细胞活化、炎性因子释放及受体表达的影响。方法 8～10周龄野生型(WT)的C57BL/6健康雄性小鼠2只，取胫骨与股骨提取骨髓进行骨髓源肥大细胞(BMMCs)培养，将5 mL PBS注射至小鼠腹腔，取腹腔灌洗液以获取腹膜来源的肥大细胞(PMCs);采用S100A4蛋白与BUD处理小鼠BMMCs和PMCs,实验分为PBS组、S100A4组、BUD组及S100A4+BUD组；β-己糖胺酶(β-hex)释放实验检测细胞脱颗粒指标β-hex、ELISA测定细胞活化介质类胰蛋白酶、糜蛋白酶及白三烯B4的释放，流式细胞术编码微球芯片技术(CBA)法检测炎性因子(IL-5、IL-6、IL-13和TNF-α)分泌水平以及Toll样受体4(TLR4)和晚期糖基化终产物受体(RAGE)的表达。结果 在BMMCs与PMCs中，与PBS组相比，S100A4组培养上清中β-hex、类胰蛋白酶、白三烯B4及相关炎性因子IL-5、IL-6、IL-13和TNF-α的释放增加，细胞上TLR4和RAGE的表达上调(P<0.05);与S100A4组相比，S100A4+BUD组肥大细胞活化及炎性因子分泌明显被抑制，同时TLR4的表达下调(P<0.05),而RAGE的表达无显著变化(P>0.05)。结论 BUD能够抑制S100A4介导的肥大细胞活化及炎性因子释放，并下调TLR4的表达，但不影响RAGE的表达，BUD可能通过TLR-4受体发挥其功能，为BUD在过敏性炎症中的应用提供新的理论依据。
Abstract：Objective To investigate the effects of budesonide(BUD) on S100A4-induced mast cell activation, release of inflammatory factors, and receptor expression. Methods Bone marrow was extracted from the tibiae and femurs of two 8-10-week-old wild-type(WT) C57BL/6 healthy male mice to culture bone marrow-derived mast cells(BMMCs). Peritoneal lavage was performed by injecting 5 mL of PBS into the mouse peritoneal cavity to obtain peritoneal mast cells(PMCs). Mouse BMMCs and PMCs were treated with S100A4 protein and BUD. The experiment was divided into PBS group, S100A4 group, BUD group, and S100A4+BUD group. The β-hexosaminidase(β-hex) release assay was used to measure the degranulation marker β-hex. ELISA was used to determine the release of activation mediators tryptase, chymase, and leukotriene B4. Cytokine bead array(CBA) flow cytometry was used to detect the secretion levels of inflammatory factors(IL-5, IL-6, IL-13, and TNF-α) and the expression of Toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE). Results In both BMMCs and PMCs, compared with the PBS group, the S100A4 group showed increased release of β-hex, tryptase, leukotriene B4, and the related inflammatory factors IL-5, IL-6, IL-13, and TNF-α in the culture supernatant, as well as upregulated expression of TLR4 and RAGE on the cells(P<0.05). Compared with the S100A4 group, the S100A4+BUD group showed significant inhibition of mast cell activation and inflammatory factor secretion, along with downregulated expression of TLR4(P<0.05), while the expression of RAGE showed no significant change(P>0.05). Conclusion BUD can inhibit S100A4-mediated mast cell activation and inflammatory factor release, and downregulate the expression of TLR4, but does not affect the expression of RAGE. BUD may exert its function through the TLR-4 receptor, providing a new theoretical basis for the application of BUD in allergic inflammation.
[1] KELLY G,IDUBOR O I,BINNEY S,et al.The impact of climate change on asthma and allergic-immunologic disease[J].Curr Allergy Asthma Rep,2023,23(8):453-461.
[2] GANGWAR R S,LANDOLINA N,ARPINATI L,et al.Mast cell and eosinophil surface receptors as targets for anti-allergic therapy[J].Pharmacol Ther,2017,170:37-63.
[3] LYONS J J,YI T.Mast cell tryptases in allergic inflammation and immediate hypersensitivity[J].Curr Opin Immunol,2021,72:94-106.
[4] VLIAGOFTIS H,BEFUS A D.Rapidly changing perspectives about mast cells at mucosal surfaces[J].Immunol Rev,2005,206:190-203.
[5] VALENT P,AKIN C,HARTMANN K,et al.Mast cells as a unique hematopoietic lineage and cell system:from Paul Ehrlich's visions to precision medicine concepts[J].Theranostics,2020,10(23):10743-10768.
[6] BANAFEA G H,BAKHASHAB S,ALSHAIBI H F,et al.The role of human mast cells in allergy and asthma[J].Bioengineered,2022,13(3):7049-7064.
[7] GANGWAR R S,FRIEDMAN S,SEAF M,et al.Mast cells and eosinophils in allergy:close friends or just neighbors[J].Eur J Pharmacol,2016,778:77-83.
[8] AMBARTSUMIAN N,GRIGORIAN M.S100A4,a link between metastasis and inflammation[J].Mol Biol (Mosk),2016,50(4):577-588.
[9] SAKIC A,CHAABANE C,AMBARTSUMIAN N,et al.Neutralization of S100A4 induces stabilization of atherosclerotic plaques:role of smooth muscle cells[J].Cardiovasc Res,2022,118(1):141-155.
[10]KURAMOCHI M,IZAWA T,PERVIN M,et al.The kinetics of damage-associated molecular patterns (DAMPs) and toll-like receptors during thioacetamide-induced acute liver injury in rats[J].Exp Toxicol Pathol,2016,68(8):471-477.
[11]SHIHUI M,SHIRONG Y,JING L,et al.S100A4 reprofiles lipid metabolism in mast cells via RAGE and PPAR-gamma signaling pathway[J].Int Immunopharmacol,2024,128:111555.
[12]BRUHN S,FANG Y,BARRENAS F,et al.A generally applicable translational strategy identifies S100A4 as a candidate gene in allergy[J].Sci Transl Med,2014,6(218):218ra4.
[13]WU T,MA L,JIN X,et al.S100A4 is critical for a mouse model of allergic asthma by impacting mast cell activation[J].Front Immunol,2021,12:692733.
[14]林秋力.BUD联合复方异丙托溴铵雾化治疗小儿支气管肺炎的临床效果[J].中国医药指南，2025,23(4):95-97.
[15]MUKHERJEE A B,ZHANG Z.Allergic asthma:influence of genetic and environmental factors[J].J Biol Chem,2011,286(38):32883-32889.
[16]SIDDIQUI Z A,WALKER A,PIRWANI M M,et al.Allergic rhinitis:diagnosis and management[J].Br J Hosp Med (Lond),2022,83(2):1-9.
[17]KOLKHIR P,ELIEH-ALI-KOMI D,METZ M,et al.Understanding human mast cells:lesson from therapies for allergic and non-allergic diseases[J].Nat Rev Immunol,2022,22(5):294-308.
[18]吴通前，金筱茜，马岚，等.钙结合蛋白S100A4调节小鼠骨髓源肥大细胞活化的作用[J].贵州医科大学学报，2020,45(12):1365-1370.
[19]ZHANG J,HOU S,GU J,et al.S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis[J].Oncoimmunology,2018,7(8):e1461301.
[20]FLAYER C H,GE M Q,HWANG J W,et al.Ozone inhalation attenuated the effects of budesonide on aspergillus fumigatus-induced airway inflammation and hyperreactivity in mice[J].Front Immunol,2019,10:2173.
[21]CHEN F,LIANG L,CHU F F,et al.Effects of omalizumab combined with budesonide formoterol on clinical efficacy,pulmonary function,immune function,and adverse reactions in children with moderate and severe allergic asthma[J].Allergol Immunopathol (Madr),2023,51(4):182-188.
[22]黄竹芸，章彦文，门钟兰，等.噻唑类化合物硝唑尼特联合BUD给药对卵清蛋白诱导的小鼠哮喘的治疗作用[J].广东化工，2025,52(4):60-62.
[23]ARIZONO N,KASUGAI T,YAMADA M,et al.Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats[J].Blood,1993,81(10):2572-2578.
[24]MEURER S K,NESS M,WEISKIRCHEN S,et al.Isolation of mature (peritoneum-derived) mast cells and immature (bone marrow-derived) mast cell precursors from mice[J].PLoS One,2016,11(6):e158104.
[25]O'REILLY S.S100A4 a classical DAMP as a therapeutic target in fibrosis[J].Matrix Biol,2024,127:1-7.
[26]PARK W Y,GRAY J M,HOLEWINSKI R J,et al.Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway[J].Nat Cancer,2023,4(3):419-435.
[27]HE J J,WU T Q,YAN S R,et al.S100A4 promotes experimental autoimmune encephalomyelitis by impacting microglial inflammation through TLR4/NF-kappaB signaling pathway[J].Int Immunopharmacol,2024,142(Pt A):112849.
基本信息:
DOI：10.19367/j.cnki.2096-8388.2026.01.005
中图分类号:R965
引用信息:
[1]陶甜,杨茂婕,潘忍,等.布地奈德抑制S100A4诱导的肥大细胞活化及受体表达[J].贵州医科大学学报,2026,51(01):49-56.DOI:10.19367/j.cnki.2096-8388.2026.01.005.
基金信息:
国家自然科学基金项目(82260324,82201968); 贵州省基础研究计划项目(黔科合基础-ZK[2023]一般394,黔科合基础-ZK[2023]一般398,黔科合基础-ZK[2025]面上442); 贵州省卫健委科学技术基金项目(2025GZWJKJXM1401); 贵州省2023年大学生创新训练项目(S202310660012)
2026-01-19
2026-01-19