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
Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China
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.
JIANG Wen,SHI Ding-Hua,HE Yan-Juan et al. 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]. CJCP, 2023, 25(5): 521-526.
JIANG Wen,SHI Ding-Hua,HE Yan-Juan et al. 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]. CJCP, 2023, 25(5): 521-526.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
