Objective To investigate the role of Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) pathway in lipid metabolism of alveolar macrophages in the silicosis model of rats induced by silicon dioxide (SiO2). Methods According to the random number table method, 36 SD rats were randomly divided into a normal group, a model group and an inhibitor group. The model group and the inhibitor group were modeled by slowly instilling 1 mL of silica suspension into the disposable trachea. After successful modeling, the rats in the inhibitor group were injected with TAK-242 (TLR4/NF-κB signal specific inhibitor) daily with the dose of 0.5 mg/kg. The rats in the normal group and model group were injected an equal dose of normal saline. After 4 weeks, the rats were sacrificed to collect bronchial lavage fluid (BALF). Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in BALF of each group of rats. Alveolar macrophages in BALF were extracted and cultured. Oil red O staining was used to observe the lipid droplet formation of macrophages in each group. Western blot was used to detect the expression levels of TLR4, MyD88, and NF-κB in macrophages. Results Compared with the normal group, the content of IL-6 and TNF-α in the BALF in the model group and the inhibitor group, the proportion of oil red O positive macrophages, the expression of TLR4, MyD88, and NF-κB in phagocytes all significantly increased, and the differences were statistically significant (all P<0.05). Compared with the model group, the content of IL-6 and TNF-α in BALF in the inhibitor group, the proportion of oil red O positive in macrophages, the expression of TLR4, MyD88, NF-κB in macrophages significantly reduced, the differences were statistically significant (all P<0.05). Conclusions In the silicosis model of rats caused by SiO2, TLR4/NF-κB signal is involved in the regulation of lipid metabolism of alveolar macrophages, and inhibit the expression of TLR4/NF-κB signal, which can significantly inhibit the pathological damage of silicosis.
Key words
Toll like receptor4/ nuclear factor-κB signaling pathway; /
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Silicosis model induced by silicon dioxide (SiO2); /
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Alveolar macrophages; /
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Lipid metabolism
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References
[1] Bukovitz B, Meiman J, Anderson H, et al. Silicosis: diagnosis and medicolegal implications[J]. J Forensic Sci, 2019, 64(5): 1389-1398. DOI: 10.1111/1556-4029.14048.
[2] Ophir N, Shai AB, Korenstein R, et al. Functional, inflammatory and interstitial impairment due to artificial stone dust ultrafine particles exposure[J]. Occup Environ Med, 2019, 76(12): 875-879. DOI: 10.1136/oemed-2019-105711.
[3] Wang D, Hao CF, Zhang L, et al. Exosomal miR-125a-5p derived from silica-exposed macrophages induces fibroblast transdifferentiation[J]. Ecotoxicol Environ Saf, 2020, 192(1): 110253-110263. DOI: 10.1016/j.ecoenv.2020.110253.
[4] Zhang ZQ, Zhang CZ, Shao B, et al. Effects of abnormal expression of fusion and fission genes on the morphology and function of lung macrophage mitochondria in SiO2-induced silicosis fibrosis in rats in vivo[J]. Toxicol Lett, 2019, 312(9): 181-187. DOI: 10.1016/j.toxlet.2019.04.029.
[5] Hou XM, Summer R, Chen ZY, et al. Lipid uptake by alveolar macrophages drives fibrotic responses to silica dust[J]. Sci Rep, 2019, 9(1): 399-412. DOI: 10.1038/s41598-018-36875-2.
[6] Hegde B, Bodduluri SR, Satpathy SR, et al. Inflammasome-independent leukotriene B4 production drives crystalline silica-induced sterile inflammation[J]. J Immunol, 2018, 200(10): 3556-3567. DOI: 10.4049/jimmunol.1701504.
[7] Pan W, Xu XH, Wang Y, et al. Interleukin-35 reduces inflammation in acute lung injury through inhibiting TLR4/NF-κB signaling pathways[J]. Exp Ther Med, 2020, 19(3): 1695-1700. DOI: 10.3892/etm. 2020. 8407.
[8] 陆青兰, 黄世稳, 韦雪平, 等. 黄根多糖对大鼠矽肺纤维化的作用[J]. 中草药, 2020, 51(4): 1031-1036. DOI: 10.7501/j.issn.0253-2670. 2020. 04.029.
[9] 颜君, 于春锐, 孙立新, 等. 盐酸戊乙奎醚对大鼠呼吸机相关性肺损伤时气道MUC5AC表达的影响及其与TLR4/MyD88信号通路的关系[J]. 中华麻醉学杂志, 2019, 39(10): 1248-1252. DOI: 10.3760∕cma.j.issn.0254-1416.2019.10.025.
[10]Giannakis N, Sansbury BE, Patsalos A, et al. Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration[J]. Nat Immunol, 2019, 20(5): 626-636. DOI: 10.1038/s41590-019-0356-7.
[11]黄鸿波, 庄锡彬, 郑锦阳, 等. 矽肺合并机化性肺炎119例临床诊断与治疗[J]. 环境与职业医学, 2019, 36(8): 761-766. DOI: 10.13213/j.cnki.jeom.2019.19125.
[12]赵娜, 吴洁, 吴奇峰, 等. 矽肺患者血清甘露聚糖结合凝集素与Th17/Treg关系[J]. 中国职业医学, 2019, 46(3): 263-268. DOI: 10.11763/j.issn.2095-2619.2019.03.001.
[13]Du ST, Li C, Lu YP, et al. Dioscin alleviates crystalline silica-induced pulmonary inflammation and fibrosis through promoting alveolar macrophage autophagy[J]. Theranostics, 2019, 9(7): 1878-1892. DOI: 10.7150/thno.29682.
[14]Fang SC, Guo HF, Cheng YS, et al. circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1[J]. Cell Death Dis, 2018, 9(3): 396-412. DOI: 10.1038/s41419-018-0432-1.
[15]Jiang KF, Yang J, Guo S, et al. Peripheral circulating exosome-mediated delivery of miR-155 as a novel mechanism for acute lung inflammation[J]. Mol Ther, 2019, 27(10): 1758-1771. DOI: 10.1016/j.ymthe. 2019. 07.003.
[16]Liu J, Chen T, Lei P, et al. Exosomes released by bone marrow mesenchymal stem cells attenuate lung injury induced by intestinal ischemia reperfusion via the TLR4/NF-κB pathway[J]. Int J Med Sci, 2019, 16(9): 1238-1244. DOI: 10.7150/ijms.35369.
[17]Wang YF, Zhang XR, Tian JM, et al. Sevoflurane alleviates LPS‑induced acute lung injury via the microRNA‑27a‑3p/TLR4/MyD88/NF‑κB signaling pathway[J]. Int J Mol Med, 2019, 44(2): 479-490. DOI: 10.3892/ijmm.2019.4217.
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