|
|
Hydrogen therapy promotes macrophage polarization to the M2 subtype by inhibiting the NF-κB signaling pathway |
GAO Xue1,2, NIU Shiying1,3, SONG Guohua2, LI Lulu2, ZHANG Xiaoyue1, PAN Wentao2, CAO Xuetao1,2, ZHANG Xinhui1,2, SUN Meili4, ZHAO Guoli5, ZHANG Yueying1,2 |
1. Department of Pathology, The First Affiliated Hospital of Shandong First Medical University, Jinan 250117 China; 2. Department of Pathophysiology, School of Clinical and Basic Medicine, Shandong First Medical University, Jinan 250117 China; 3. Department of Pathology, Linfen Central Hospital, Shanxi Province, Linfen 041000 China; 4. Department of Oncology, Affiliated Central Hospital of Shandong First Medical University, Jinan 250117 China; 5. Department of Pathology, Liaocheng Infectious Disease Hospital, Liaocheng 252000 China |
|
|
Abstract Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.
|
Received: 19 August 2023
|
|
|
|
|
[1] Giuranno L, Ient J, De Ruysscher D, et al. Radiation-induced lung injury (RILI)[J]. Front Oncol, 2019, 9: 877. DOI: 10.3389/fonc.2019.00877 [2] Niu SY, Zhang YH, Cong CS, et al. Comparative study of radiation-induced lung injury model in two strains of mice[J]. Health Phys, 2022, 122(5): 579-585. DOI: 10.1097/HP.0000000000001532 [3] Chen ZJ, Wu ZQ, Ning W. Advances in molecular mechanisms and treatment of radiation-induced pulmonary fibrosis[J]. Transl Oncol, 2019, 12(1): 162-169. DOI: 10.1016/j.tranon.2018.09.009 [4] Li JL, Wang R, Shi W, et al. Epigenetic regulation in radiation-induced pulmonary fibrosis[J]. Int J Radiat Biol, 2023, 99(3): 384-395. DOI: 10.1080/09553002.2022.2089365 [5] Arroyo-Hernández M, Maldonado F, Lozano-Ruiz F, et al. Radiation-induced lung injury: current evidence[J]. BMC Pulm Med, 2021, 21(1): 9. DOI: 10.1186/s12890-020-01376-4 [6] Zhou KX, Liu M, Wang YB, et al. Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: a systematic review and meta-analysis[J]. Front Nutr, 2023, 10: 1094767. DOI: 10.3389/fnut.2023.1094767 [7] Liu BY, Xie YB, Chen J, et al. Protective effect of molecular hydrogen following different routes of administration on D-galactose-induced aging mice[J]. J Inflamm Res, 2021, 14: 5541-5550. DOI: 10.2147/JIR.S332286 [8] Yan YJ, Fu JM, Kowalchuk RO, et al. Exploration of radiation-induced lung injury, from mechanism to treatment: a narrative review[J]. Transl Lung Cancer Res, 2022, 11(2): 307-322. DOI: 10.21037/tlcr-22-108 [9] Yan YJ, Wu LL, Li XF, et al. Immunomodulatory role of azithromycin: potential applications to radiation-induced lung injury[J]. Front Oncol, 2023, 13: 966060. DOI: 10.3389/fonc.2023.966060 [10] Shrishrimal S, Kosmacek EA, Oberley-Deegan RE. Reactive oxygen species drive epigenetic changes in radiation-induced fibrosis[J]. Oxid Med Cell Longev, 2019, 2019: 4278658. DOI: 10.1155/2019/4278658 [11] 耿爽, 李倩, 郗停停, 等. 补体在放射性肺损伤中的作用与机制[J]. 中国辐射卫生,2022,31(5):535-541. DOI: 10.13491/j.issn.1004-714X.2022.05.002 Geng S, Li Q, Xi TT, et al. Role of complement in radiation-induced lung injury[J]. Chin J Radiol Health, 2022, 31(5): 535-541. DOI: 10.13491/j.issn.1004-714X.2022.05.002 [12] 陈家祯, 王玉, 王存良, 等. 放射性肺损伤发病机制及分子靶向治疗研究进展[J]. 中国辐射卫生,2021,30(3):377-380,390. DOI: 10.13491/j.issn.1004-714X.2021.03.023 Chen JZ, Wang Y, Wang CL, et al. Research progress on pathogenesis and molecular targeted therapy of radiation-induced lung injury[J]. Chin J Radiol Health, 2021, 30(3): 377-380,390. DOI: 10.13491/j.issn.1004-714X.2021.03.023 [13] Beach TA, Finkelstein JN, Chang PY. Epithelial responses in radiation-induced lung injury (RILI) allow chronic inflammation and fibrogenesis[J]. Radiat Res, 2023. DOI: 10.1667/RADE-22-00130.1. [14] Ying HJ, Fang M, Chen M. Progress in the mechanism of radiation-induced lung injury[J]. Chin Med J, 2021, 134(2): 161-163. DOI: 10.1097/CM9.0000000000001032 [15] Hanania AN, Mainwaring W, Ghebre YT, et al. Radiation-induced lung injury: assessment and management[J]. Chest, 2019, 156(1): 150-162. DOI: 10.1016/j.chest.2019.03.033 [16] Dumbuya JS, Li SQ, Liang LL, et al. Effects of hydrogen-rich saline in neuroinflammation and mitochondrial dysfunction in rat model of sepsis-associated encephalopathy[J]. J Transl Med, 2022, 20(1): 546. DOI: 10.1186/s12967-022-03746-4 [17] Yu MD, Qin C, Li P, et al. Hydrogen gas alleviates sepsis-induced neuroinflammation and cognitive impairment through regulation of DNMT1 and DNMT3a-mediated BDNF promoter IV methylation in mice[J]. Int Immunopharmacol, 2021, 95: 107583. DOI: 10.1016/j.intimp.2021.107583 [18] Ohsawa I. Biological responses to hydrogen molecule and its preventive effects on inflammatory diseases[J]. Curr Pharm Des, 2021, 27(5): 659-666. DOI: 10.2174/1381612826666200925123510 [19] Terasaki Y, Ohsawa I, Terasaki M, et al. Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress[J]. Am J Physiol Lung Cell Mol Physiol, 2011, 301(4): L415-L426. DOI: 10.1152/ajplung.00008.2011 [20] Viola A, Munari F, Sánchez-Rodríguez R, et al. The metabolic signature of macrophage responses[J]. Front Immunol, 2019, 10: 1462. DOI: 10.3389/fimmu.2019.01462 [21] Yahyapour R, Shabeeb D, Cheki M, et al. Radiation protection and mitigation by natural antioxidants and flavonoids: implications to radiotherapy and radiation disasters[J]. Curr Mol Pharmacol, 2018, 11(4): 285-304. DOI: 10.2174/1874467211666180619125653 [22] Alharbi KS, Fuloria NK, Fuloria S, et al. Nuclear factor-kappa B and its role in inflammatory lung disease[J]. Chem Biol Interact, 2021, 345: 109568. DOI: 10.1016/j.cbi.2021.109568 [23] Zhang Q, Mao ZJ, Sun J. NF-κB inhibitor, BAY11-7082, suppresses M2 tumor-associated macrophage induced EMT potential via miR-30a/NF-κB/Snail signaling in bladder cancer cells[J]. Gene, 2019, 710: 91-97. DOI: 10.1016/j.gene.2019.04.039 [24] Li T, Li L, Peng RL, et al. Abrocitinib attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting the JAK1/STAT1/NF-κB pathway[J]. Cells, 2022, 11(22): 3588. DOI: 10.3390/cells11223588
|
[1] |
ZHANG Xinhui, NIU Shiying, YAO Shutong, ZHANG Xiaoyue, CAO Xuetao, GAO Xue, ZHAO Guoli, CHEN Jingkun, ZHANG Yueying. BMSCs promote M2 macrophage polarization to attenuate acute radiation-induced lung injury[J]. Chinese Journal of Radiological Health, 2024, 33(1): 21-27. |
|
|
|
|