Effect of procalcitonin on lipopolysaccharide-induced expression of nucleotide-binding oligomerization domain-like receptor protein 3 and caspase-1 in human umbilical vein endothelial cells

JIANG Wen; SHI Ding-Hua; HE Yan-Juan; CHEN Chun-Yuan

doi:10.7499/j.issn.1008-8830.2301031

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Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (5) : 521-526. DOI: 10.7499/j.issn.1008-8830.2301031

EXPERIMENTAL RESEARCH

Effect of procalcitonin on lipopolysaccharide-induced expression of nucleotide-binding oligomerization domain-like receptor protein 3 and caspase-1 in human umbilical vein endothelial cells

JIANG Wen, SHI Ding-Hua, HE Yan-Juan, CHEN Chun-Yuan

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Abstract

Objective To study the effect of procalcitonin (PCT) on lipopolysaccharide (LPS)-induced expression of the pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and caspase-1 in human umbilical vein endothelial cells (HUVECs). Methods HUVECs were induced by LPS to establish a model of sepsis-induced inflammatory endothelial cell injury. The experiment was divided into two parts. In the first part, HUVECs were randomly divided into four groups: normal control, LPS (1 μg/mL), PCT (10 ng/mL), and LPS+PCT (n=3 each). In the second part, HUVECs were randomly grouped: normal control, LPS, and LPS+PCT of different concentrations (0.1, 1, 10, and 100 ng/mL) (n=3 each). Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of NLRP3 and caspase-1 in each group. Results In the first experiment: compared with the normal control group, the PCT, LPS, and LPS+PCT groups had significantly upregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05); compared with the LPS group, the LPS+PCT group had significantly downregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05). In the second experiment: compared with those in the LPS group, the mRNA and protein expression levels of NLRP3 and caspase-1 in the LPS+PCT of different concentrations groups were significantly downregulated in a concentration-dependent manner (P<0.05). Conclusions LPS can promote the expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs, while PCT can inhibit the LPS-induced expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs in a concentration-dependent manner.

Key words

Sepsis / Procalcitonin / Pyroptosis / Nucleotide-binding oligomerization domain-like receptor protein 3 / Caspase-1 / Human umbilical vein endothelial cell

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JIANG Wen, SHI Ding-Hua, HE Yan-Juan, CHEN Chun-Yuan. Effect of procalcitonin on lipopolysaccharide-induced expression of nucleotide-binding oligomerization domain-like receptor protein 3 and caspase-1 in human umbilical vein endothelial cells[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(5): 521-526 https://doi.org/10.7499/j.issn.1008-8830.2301031

References

1 Schlapbach LJ. Paediatric sepsis[J]. Curr Opin Infect Dis, 2019, 32(5): 497-504. PMID: 31335441. DOI: 10.1097/QCO.0000000000000583.
2 Emr BM, Alcamo AM, Carcillo JA, et al. Pediatric sepsis update: how are children different?[J]. Surg Infect (Larchmt), 2018, 19(2): 176-183. PMID: 29394150. DOI: 10.1089/sur.2017.316.
3 Garcia PCR, Tonial CT, Piva JP. Septic shock in pediatrics: the state-of-the-art[J]. J Pediatr (Rio J), 2020, 96(Suppl 1):87-98. PMID: 31843507. PMCID: PMC9432279. DOI: 10.1016/j.jped.2019.10.007.
4 Uchimido R, Schmidt EP, Shapiro NI. The glycocalyx: a novel diagnostic and therapeutic target in sepsis[J]. Crit Care, 2019, 23(1): 16. PMID: 30654825. PMCID: PMC6337861. DOI: 10.1186/s13054-018-2292-6.
5 Iba T, Levy JH. Derangement of the endothelial glycocalyx in sepsis[J]. J Thromb Haemost, 2019, 17(2):283-294. PMID: 30582882. DOI: 10.1111/jth.14371.
6 Li ZF, Wang YC, Feng QR, et al. Inhibition of the C3a receptor attenuates sepsis-induced acute lung injury by suppressing pyroptosis of the pulmonary vascular endothelial cells[J]. Free Radic Biol Med, 2022, 184: 208-217. PMID: 35367342. DOI: 10.1016/j.freeradbiomed.2022.02.032.
7 Le KTT, Chu X, Jaeger M, et al. Leukocyte-released mediators in response to both bacterial and fungal infections trigger IFN pathways, independent of IL-1 and TNF-α, in endothelial cells[J]. Front Immunol, 2019, 10: 2508. PMID: 31708927. PMCID: PMC6824321. DOI: 10.3389/fimmu.2019.02508.
8 Chang JC. Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease[J]. Thromb J, 2019, 17:10. PMID: 31160889. PMCID: PMC6542012. DOI: 10.1186/s12959-019-0198-4.
9 Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death[J]. Cell Mol Immunol, 2021, 18(5): 1106-1121. PMID: 33785842. PMCID: PMC8008022. DOI: 10.1038/s41423-020-00630-3.
10 Li S, Sun Y, Song M, et al. NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression[J]. JCI insight, 2021, 6(23): e146852. PMID: 34877938. PMCID: PMC8675200. DOI: 10.1172/jci.insight.146852.
11 Qu M, Wang Y, Qiu Z, et al. Necroptosis, pyroptosis, ferroptosis in sepsis and treatment[J]. Shock, 2022, 57(6): 161-171. PMID: 35759299. DOI: 10.1097/SHK.0000000000001936.
12 Wen R, Liu YP, Tong XX, et al. Molecular mechanisms and functions of pyroptosis in sepsis and sepsis-associated organ dysfunction[J]. Front Cell Infect Microbiol, 2022, 12: 962139. PMID: 35967871, PMCID: PMC9372372, DOI: 10.3389/fcimb.2022.962139.
13 Velissaris D, Zareifopoulos N, Lagadinou M, et al. Procalcitonin and sepsis in the emergency department: an update[J]. Eur Rev Med Pharmacol Sci, 2021, 25(1): 466-479. PMID: 33506938. DOI: 10.26355/eurrev_202101_24416.
14 Downes KJ, Fitzgerald JC, Weiss SL. Utility of procalcitonin as a biomarker for sepsis in children[J]. J Clin Microbiol, 2020, 58(7): e01851-19. PMID: 32350044. PMCID: PMC7315022. DOI: 10.1128/JCM.01851-19.
15 Long D, Yang J, Wu X, et al. Urokinase-type plasminogen activator protects human umbilical vein endothelial cells from apoptosis in sepsis. Int J Clin Exp Pathol, 2019, 12(1): 77-86. PMID: 31933722; PMCID:PMC6944024.
16 Joffre J, Hellman J, Ince C, et al. Endothelial responses in sepsis[J]. Am J Respir Crit Care Med, 2020, 202(3): 361-370. PMID: 32101446. DOI: 10.1164/rccm.201910-1911TR.
17 Pons S, Arnaud M, Loiselle M, et al. Immune consequences of endothelial cells' activation and dysfunction during sepsis[J]. Crit Care Clin, 2020, 36(2): 401-413. PMID: 32172821. DOI: 10.1016/j.ccc.2019.12.001.
18 Wang Q, Wu J, Zeng Y, et al. Pyroptosis: a pro-inflammatory type of cell death in cardiovascular disease[J]. Clin Chim Acta, 2020, 510: 62-72. PMID: 32622968. DOI: 10.1016/j.cca.2020.06.044.
19 Li Z, Jia Y, Feng Y, et al. Methane alleviates sepsis-induced injury by inhibiting pyroptosis and apoptosis: in vivo and in vitro experiments[J]. Aging (Albany NY), 2019, 11(4): 1226-1239. PMID: 30779706. PMCID: PMC6402521. DOI: 10.18632/aging.101831.
20 Du T, Gao J, Li P, et al. Pyroptosis, metabolism, and tumor immune microenvironment[J]. Clin Transl Med, 2021, 11(8): e492. PMID: 34459122. PMCID: PMC8329701. DOI: 10.1002/ctm2.492.
21 Hsu SK, Li CY, Lin IL, et al. Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment[J]. Theranostics, 2021, 11(18): 8813-8835. PMID: 34522213. PMCID: PMC8419056. DOI: 10.7150/thno.62521.
22 Mitra S, Exline M, Habyarimana F, et al. Microparticulate caspase 1 regulates gasdermin D and pulmonary vascular endothelial cell injury[J]. Am J Respir Cell Mol Biol, 2018, 59(1): 56-64. PMID: 29365280. PMCID: PMC6039876. DOI: 10.1165/rcmb.2017-0393OC.
23 Sauer M, Do? S, Ehler J, et al. Procalcitonin impairs liver cell viability and function in vitro: a potential new mechanism of liver dysfunction and failure during sepsis?[J]. Biomed Res Int, 2017, 2017: 6130725. PMID: 28255555. PMCID: PMC5309405. DOI: 10.1155/2017/6130725.
24 Rule JA, Hynan LS, Attar N, et al. Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure[J]. PLoS One, 2015, 10(9):e0138566. PMID: 26393924. PMCID: PMC4579124. DOI: 10.1371/journal.pone.0138566.
25 Kalbitz M, Fattahi F, Grailer JJ, et al. Complement-induced activation of the cardiac NLRP3 inflammasome in sepsis[J]. FASEB J, 2016, 30(12):3997-4006. PMID: 27543123. PMCID: PMC5102118. DOI: 10.1096/fj.201600728R.
26 Toldo S, Mauro AG, Cutter Z, et al. Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury[J]. Am J Physiol Heart Circ Physiol, 2018, 315(6): H1553-H1568. PMID: 30168729. PMCID: PMC6336966. DOI: 10.1152/ajpheart.00158.2018.
27 Kobayashi H, Amrein K, Lasky-Su JA, et al. Procalcitonin metabolomics in the critically ill reveal relationships between inflammation intensity and energy utilization pathways[J]. Sci Rep, 2021, 11(1): 23194. PMID: 34853395. PMCID: PMC8636627. DOI: 10.1038/s41598-021-02679-0.
28 Hoffmann G, Schobersberger W. Anti-inflammatory procalcitonin (PTC) in a human whole blood model septic shock[J]. Cytokine, 2001, 14(2): 127-128. PMID: 11356014. DOI: 10.1006/cyto.2000.0853.
29 Monneret G, Pachot A, Laroche B, et al. Procalcitonin and calcitonin gene-related peptide decrease LPS-induced tnf production by human circulating blood cells[J]. Cytokine, 2000, 12(6): 762-764. PMID: 10843760. DOI: 10.1006/cyto.1999.0607.
30 Hoffmann G, Czechowski M, Schloesser M, et al. Procalcitonin amplifies inducible nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle cells[J]. Crit Care Med, 2002, 30(9): 2091-2095. PMID: 12352046. DOI: 10.1097/00003246-200209000-00023.