Spermidine reduces LPS-induced ALI by inhibiting the NF-&#x003ba;B/ NLRP3 inflammasome pathway

LUO Yutao; SU Qing; LI Rui; YANG Rui; ZHENG Tongqi; WEI Yunfu; SUN Guoying

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Journal of Hunan Normal University(Medical Science) ›› 2023, Vol. 20 ›› Issue (1) : 6-12.

Basic Medicine

Spermidine reduces LPS-induced ALI by inhibiting the NF-κB/ NLRP3 inflammasome pathway

LUO Yutao¹, SU Qing², LI Rui³, YANG Rui³, ZHENG Tongqi³, WEI Yunfu¹, SUN Guoying¹

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Abstract

Objective The purpose of this study was to observe the effect of spermidine on the expression and activation of NLRP3 in lipopolysaccharide (LPS) - induced acute lung injury (ALI) mice. Methods Effectof spermidine on respiratory function in ALI mice was detected by a small animal ventilator, and the survival rate of mice was detected. Pathological score were used to evaluate the effect of spermidine on the morphological changes of lung tissue in ALI mice, and levels of IL-1β and IL-18 protein levels in bronchoalveolar lavage fluid (BALF) of ALI mice were detectd by ELISA. The qPCR was used to detect the expression of IL-1β, IL-18, NLRP3, ASC, pro-caspase-1 and NF-κB in mouse lungs; IκB expression of mice was detected by Western blots. Results Spermidine could improve the respiratory function and survival rate of ALI mice, alleviate LPS induced lung pathological damage, and reduce IL-1β, IL-18, NLRP3, ASC, pro-caspase-1, NF-κB and IκB expression of ALI mice. Conclusions Spermidine may reduce the assembly and activation of NLRP3 inflammasome by inhibiting the activation of NF-κB in the lung tissue of ALI mice, thereby inhibit the expression of inflammatory factors, and ultimately lessening ALI. This study can provide an experimental basis for exploring the mechanism of ALI from the perspective of regulating endogenous energy metabolism.

Key words

spermidine / acute lung injury / lipopolysaccharide / inflammatory corpuscle

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LUO Yutao, SU Qing, LI Rui, YANG Rui, ZHENG Tongqi, WEI Yunfu, SUN Guoying. Spermidine reduces LPS-induced ALI by inhibiting the NF-κB/ NLRP3 inflammasome pathway[J]. Journal of Hunan Normal University(Medical Science). 2023, 20(1): 6-12

References

[1] Jin Y, Qian J, Ju X, et al.Osthole Protects against Acute Lung Injury by Suppressing NF- κ B-Dependent Inflammation[J]. Mediators Inflamm, 2018, 35(3): 1-12.
[2] Nguyen N, Xu S, Lam T YW, et al.ISM1 suppresses LPS-induced acute lung injury and post-injury lung fibrosis in mice[J]. Mol Med, 2022, 28(1): 1-17.
[3] Yang SC, Tsai YF, Pan YL, et al.Understanding the role of neutrophils in acute respiratory distress syndrome[J]. Biomed J, 2021, 44(4): 439-446.
[4] Miao EA, Leaf IA, Treuting PM, et al.Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria[J]. Nat Immunol, 2010, 11(12): 1136-1142.
[5] Deshpande R, Zou C.Pseudomonas Aeruginosa Induced Cell Death in Acute Lung Injury and Acute Respiratory Distress Syndrome[J]. Int J Mol Sci, 2020, 21(15): 5356-5362.
[6] Tzotzos SJ, Fischer B, Fischer H, et al.Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey[J]. Crit Care, 2020, 24(1): 516-523.
[7] Shi R, Radulovich N, Ng C, et al.Organoid Cultures as Preclinical Models of Non-Small Cell Lung Cancer[J]. Clin Cancer Res, 2020, 26(5): 1162-1174.
[8] Gong Y, Yu Z, Gao Y, et al.FABP4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury[J]. Biochembioph Res Co, 2018, 496(4): 1115-1121.
[9] Zhang L S, Zhang J S, Hou Y L, et al.Intermedin1-53 Inhibits NLRP3 Inflammasome Activation by Targeting IRE1α in Cardiac Fibrosis[J]. Inflammation, 2022, 45(4): 1568-1584.
[10] Guo M, An F, Yu H, et al.Comparative effects of schisandrin A, B, and C on Propionibacterium acnes-induced, NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis[J]. Biomed Pharmacother, 2017, 96(5): 129-136.
[11] Grailer J J, Canning B A, Kalbitz M, et al.Critical role for the NLRP3 inflammasome during acute lung injury[J]. J Immunol, 2014, 192(12): 5974-5983.
[12] Fukumoto J, Fukumoto I, Parthasarathy P T, et al.NLRP3 deletion protects from hyperoxia-induced acute lung injury[J]. Am J Physiol-cell Ph, 2013, 305(2): 182-189.
[13] 丁慧如, 邓心未, 刘怀存, 等. 二氢杨梅素下调大鼠缺血性脑卒中脑组织炎症小体Nod样受体蛋白3的表达[J]. 解剖学报, 2022, 53(2): 137-143.
[14] Huang J, Zhang H, Zhang J, et al.Spermidine Exhibits Protective Effects Against Traumatic Brain Injury[J]. Cell Mol Neurobiol, 2020, 40(6): 927-937.
[15] Kim J.Spermidine is protective against kidney ischemia and reperfusion injury through inhibiting DNA nitration and PARP1 activation[J]. Anat Cell Biol, 2017, 50(3): 200-206.
[16] Zhou S, Gu J, Liu R, et al.Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy[J]. Front Immunol, 2018, 9(2): 948-951.
[17] Chen Z, Lin CX, Song B, et al.Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis[J]. Cell Death Dis, 2020, 11(7): 503-509.
[18] 粟青, 曹理, 彭卓, 等. 亚精胺减轻脂多糖诱导的小鼠急性肺损伤[J]. 中国临床解剖学杂志, 2020.38(1): 62-65.
[19] Zhang X, Li C, Li J, et al.Protective effects of protocatechuic acid on acute lung injury induced by lipopolysaccharide in mice via p38MAPK and NF-κB signal pathways[J]. Int Immunopharmacol, 2015, 26(1): 229-236.
[20] Signor C, Mello CF, Porto GP, et al.Spermidine improves fear memory persistence[J]. Eur J Pharmacol, 2014, 730(5): 72-76.
[21] Nishina K, Mikawa K, Takao Y, et al.Intravenous lidocaine attenuates acute lung injury induced by hydrochloric acid aspiration in rabbits[J]. Anesthesiology, 1998, 88(5): 1300-1309.
[22] Morales-Ortíz J, Deal V, Reyes F, et al.Platelet-derived TLT-1 is a prognostic indicator in ALI/ARDS and prevents tissue damage in the lungs in a mouse model[J]. Blood, 2022, 132(23): 2495-2505.
[23] 瞿利花, 陈阳晔, 李懿, 等. 甘草酸对LPS 诱导的小鼠急性肺损伤中ACE2的影响[J]. 湖南师范大学学报医学版, 2020, 3(4): 7-10.
[24] Jiang J, Huang K, Xu S, et al.Targeting NOX4 alleviates sepsis-induced acute lung injury via attenuation of redox-sensitive activation of CaMKII/ERK1/2/MLCK and endothelial cell barrier dysfunction[J]. Redox Biol, 2020, 36(3): 638-645.
[25] Sekine K, Fujishima S, Sasaki J, et al.In vivo IL-18 supplementation ameliorates lethal acute lung injury in burn-primed endotoxemic mice: a novel anti-inflammatory role of IL-18[J]. Shock, 2009, 32(5): 554-562.
[26] Dolinay T, Kim Y S, Howrylak J, et al.Inflammasome-regulated Cytokines Are Critical Mediators of Acute Lung Injury[J]. Am J Resp Crit Care, 2012, 185(11): 1225-1234.
[27] Zhao J, Yu H, Liu Y, et al.Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury[J]. Am J Physiol Lung Cell Mol Physiol, 2016, 311(5): L868-L880.
[28] 胡天晓, 王秀景, 阮芸, 等. 高糖通过激活NLRP3炎症小体促进胎盘滋养细胞IL-1β、IL-18的释放[J]. 中华内分泌代谢杂志, 2022, 38(01): 36-41.
[29] Ao Z, Pan W, Lv J, et al.Protective Effect of Amygdalin on LPS-Induced Acute Lung Injury by Inhibiting NF-κB and NLRP3 Signaling Pathways[J]. Inflammation, 2017, 40(3): 745-751.