IL‑1β‑induced pentraxin 3 inhibits the proliferation, invasion and cell cycle of trophoblasts in preeclampsia and is suppressed by IL‑1β antagonists

Wang,Xiaoxi; Zhang,Jing; Ji,Jing

doi:10.3892/mmr.2022.12631

IL‑1β‑induced pentraxin 3 inhibits the proliferation, invasion and cell cycle of trophoblasts in preeclampsia and is suppressed by IL‑1β antagonists

Authors:
- Xiaoxi Wang
- Jing Zhang
- Jing Ji
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Maternity Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210004, P.R. China, Obstetric Ward II, The Affiliated Northwest Women's and Children's Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
Published online on: February 7, 2022 https://doi.org/10.3892/mmr.2022.12631
Article Number: 115
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Pentraxin 3 (PTX3), a member of the c‑reactive protein family, is a long pentraxin protein and a pro‑inflammatory marker. However, the role of PTX3 in preeclampsia (PE) remains to be elucidated. Thus, the present study aimed to investigate the biological role and mechanisms underlying PTX3 in PE. In the present study, PTX3 was overexpressed in trophoblasts and the subsequent changes in cell proliferation, cycle distribution and invasion were observed using Cell Counting Kit‑8, flow cytometry and Transwell assays, respectively. Moreover, the expression levels of MMP2 and MMP9, proteins associated with the development of PE, were detected using reverse transcription‑quantitative PCR and western blot analysis. Following treatment with interleukin (IL)‑1β, the expression levels of PTX3 were measured. Furthermore, subsequent changes in cell proliferation, cycle distribution and invasion were investigated following overexpression of PTX3 and treatment with IL‑1 receptor antagonist (IL‑1Ra). Overexpression of PTX3 inhibited the proliferation, cycle and invasion of HTR‑8/SV neo and JEG3 cells. Moreover, treatment with IL‑1β increased the expression of PTX3 in HTR‑8/SV neo and JEG3 cells, which was suppressed following treatment with the IL‑1β antagonist. Following PTX3 overexpression and treatment with IL‑1Ra, the inhibitory effects of PTX3 overexpression alone on the invasion of HTR‑8/SV neo and JEG3 cells were attenuated. In conclusion, these results indicated that IL‑1β could induce PTX3 upregulation, which led to the inhibition of the proliferation, invasion and cell cycle of trophoblasts, thereby promoting the progression of PE.

View Figures

View References

1	Hauth JC, Ewell MG, Levine RJ, Esterlitz JR, Sibai B, Curet LB, Catalano PM and Morris CD: Pregnancy outcomes in healthy nulliparas who developed hypertension. Calcium for preeclampsia prevention study group. Obstet Gynecol. 95:24–28. 2000. View Article : Google Scholar : PubMed/NCBI
2	Chappell LC, Cluver CA, Kingdom J and Tong S: Pre-eclampsia. Lancet. 398:341–354. 2021. View Article : Google Scholar : PubMed/NCBI
3	Barton JR and Sibai BM: Prediction and prevention of recurrent preeclampsia. Obstet Gynecol. 112:359–372. 2008. View Article : Google Scholar : PubMed/NCBI
4	Karumanchi SA: Angiogenic factors in preeclampsia: From diagnosis to therapy. Hypertension. 67:1072–1079. 2016. View Article : Google Scholar : PubMed/NCBI
5	Shaw J, Tang Z, Schneider H, Salje K, Hansson SR and Guller S: Inflammatory processes are specifically enhanced in endothelial cells by placental-derived TNF-alpha: Implications in preeclampsia (PE). Placenta. 43:1–8. 2016. View Article : Google Scholar : PubMed/NCBI
6	Harmon AC, Cornelius DC, Amaral LM, Faulkner JL, Cunningham MW Jr, Wallace K and LaMarca B: The role of inflammation in the pathology of preeclampsia. Clin Sci (Lond). 130:409–419. 2016. View Article : Google Scholar : PubMed/NCBI
7	Cotechini T, Komisarenko M, Sperou A, Macdonald-Goodfellow S, Adams MA and Graham CH: Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. J Exp Med. 211:165–179. 2014. View Article : Google Scholar : PubMed/NCBI
8	Fan M, Li X, Gao X, Dong L, Xin G, Chen L, Qiu J and Xu Y: LPS induces preeclampsia-like phenotype in rats and HTR8/SVneo cells dysfunction through TLR4/p38 MAPK pathway. Front Physiol. 10:10302019. View Article : Google Scholar : PubMed/NCBI
9	Kadam L, Kilburn B, Baczyk D, Kohan-Ghadr HR, Kingdom J and Drewlo S: Rosiglitazone blocks first trimester in-vitro placental injury caused by NF-κB-mediated inflammation. Sci Rep. 9:20182019. View Article : Google Scholar : PubMed/NCBI
10	Zaga-Clavellina V, Garcia-Lopez G, Flores-Herrera H, Espejel-Nuñez A, Flores-Pliego A, Soriano-Becerril D, Maida-Claros R, Merchant-Larios H and Vadillo-Ortega F: In vitro secretion profiles of interleukin (IL)-1beta, IL-6, IL-8, IL-10, and TNF alpha after selective infection with Escherichia coli in human fetal membranes. Reprod Biol Endocrinol. 5:462007. View Article : Google Scholar : PubMed/NCBI
11	Poston L: Endothelial dysfunction in pre-eclampsia. Pharmacol Rep. 58 (Suppl 1):S69–S74. 2006.PubMed/NCBI
12	Black KD and Morin KH: Development and testing of the preeclampsia prenatal symptom-monitoring checklist (PPSMC). J Nurs Meas. 22:14–28. 2014. View Article : Google Scholar : PubMed/NCBI
13	Anderson CM and Schmella MJ: CE: Preeclampsia: Current approaches to nursing management. Am J Nurs. 117:30–38. 2017. View Article : Google Scholar : PubMed/NCBI
14	Xiong Z, Wang X, Jiang S, Jin M and Chen W: Association between pentraxin-3 and the risk of preeclampsia: A meta-analysis. Medicine (Baltimore). 99:e207442020. View Article : Google Scholar : PubMed/NCBI
15	Napoleone E, di Santo A, Peri G, Mantovani A, de Gaetano G, Donati MB and Lorenzet R: The long pentraxin PTX3 up-regulates tissue factor in activated monocytes: Another link between inflammation and clotting activation. J Leukoc Biol. 76:203–209. 2004. View Article : Google Scholar : PubMed/NCBI
16	Akhter T, Wikstrom AK, Larsson M, Larsson A, Wikstrom G and Naessen T: Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia. Int J Cardiol. 241:417–422. 2017. View Article : Google Scholar : PubMed/NCBI
17	Ovayolu A, Turksoy VA, Ovayolu G, Ozek MA, Dogan I and Karaman E: Analyses of interleukin-6, presepsin and pentraxin-3 in the diagnosis and severity of late-onset preeclampsia. J Matern Fetal Neonatal Med. 35:299–307. 2022. View Article : Google Scholar : PubMed/NCBI
18	Turkmen O, Mollaoglu S, Goynumer G and Isbilen B: Plasma pentraxin 3 levels in preeclamptic patients. Clin Exp Obstet Gynecol. 42:220–223. 2015.PubMed/NCBI
19	Hamad RR, Eriksson MJ, Berg E, Larsson A and Bremme K: Impaired endothelial function and elevated levels of pentraxin 3 in early-onset preeclampsia. Acta Obstet Gynecol Scand. 91:50–56. 2012. View Article : Google Scholar : PubMed/NCBI
20	Popovici RM, Krause MS, Jauckus J, Germeyer A, Brum IS, Garlanda C, Strowitzki T and von Wolff M: The long pentraxin PTX3 in human endometrium: Regulation by steroids and trophoblast products. Endocrinology. 149:1136–1143. 2008. View Article : Google Scholar : PubMed/NCBI
21	Abrahams VM: The role of the Nod-like receptor family in trophoblast innate immune responses. J Reprod Immunol. 88:112–117. 2011. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Kaya B, Nayki U, Nayki C, Ulug P, Oner G, Gultekin E and Yildirim Y: Proliferation of trophoblasts and Ki67 expression in preeclampsia. Arch Gynecol Obstet. 291:1041–1046. 2015. View Article : Google Scholar : PubMed/NCBI
24	Fathipour V, Khaki Z and Nassiri SM: Evaluation of matrix metalloproteinases (MMP)-2 and MMP-9 activity in serum and biochemical and hematological parameters in spontaneous canine cutaneous tumors before and after surgical treatment. Vet Res Forum. 9:19–26. 2018.PubMed/NCBI
25	Li W, Mata KM, Mazzuca MQ and Khalil RA: Altered matrix metalloproteinase-2 and −9 expression/activity links placental ischemia and anti-angiogenic sFlt-1 to uteroplacental and vascular remodeling and collagen deposition in hypertensive pregnancy. Biochem Pharmacol. 89:370–385. 2014. View Article : Google Scholar : PubMed/NCBI
26	Shimonovitz S, Hurwitz A, Dushnik M, Anteby E, Geva-Eldar T and Yagel S: Developmental regulation of the expression of 72 and 92 kd type IV collagenases in human trophoblasts: A possible mechanism for control of trophoblast invasion. Am J Obstet Gynecol. 171:832–838. 1994. View Article : Google Scholar : PubMed/NCBI
27	Prutsch N, Fock V, Haslinger P, Haider S, Fiala C, Pollheimer J and Knöfler M: The role of interleukin-1β in human trophoblast motility. Placenta. 33:696–703. 2012. View Article : Google Scholar : PubMed/NCBI
28	Bonacina F, Moregola A, Porte R, Baragetti A, Bonavita E, Salatin A, Grigore L, Pellegatta F, Molgora M, Sironi M, et al: Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity. Cardiovasc Res. 115:1861–1872. 2019. View Article : Google Scholar : PubMed/NCBI
29	Muller B, Peri G, Doni A, Torri V, Landmann R, Bottazzi B and Mantovani A: Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients. Crit Care Med. 29:1404–1407. 2001. View Article : Google Scholar : PubMed/NCBI
30	Mauri T, Bellani G, Patroniti N, Coppadoro A, Peri G, Cuccovillo I, Cugno M, Iapichino G, Gattinoni L, Pesenti A and Mantovani A: Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality. Intensive Care Med. 36:621–629. 2010. View Article : Google Scholar : PubMed/NCBI
31	Mauri T, Coppadoro A, Bellani G, Bombino M, Patroniti N, Peri G, Mantovani A and Pesenti A: Pentraxin 3 in acute respiratory distress syndrome: An early marker of severity. Crit Care Med. 36:2302–2308. 2008. View Article : Google Scholar : PubMed/NCBI
32	Huppertz B: The critical role of abnormal trophoblast development in the etiology of preeclampsia. Curr Pharm Biotechnol. 19:771–780. 2018. View Article : Google Scholar : PubMed/NCBI
33	Longtine MS, Chen B, Odibo AO, Zhong Y and Nelson DM: Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR. Placenta. 33:352–359. 2012. View Article : Google Scholar : PubMed/NCBI
34	Zhang X, Qi C and Lin J: Enhanced expressions of matrix metalloproteinase (MMP)-2 and −9 and vascular endothelial growth factors (VEGF) and increased microvascular density in the endometrial hyperplasia of women with anovulatory dysfunctional uterine bleeding. Fertil Steril. 93:2362–2367. 2010. View Article : Google Scholar : PubMed/NCBI
35	Mishra B, Kizaki K, Koshi K, Ushizawa K, Takahashi T, Hosoe M, Sato T, Ito A and Hashizume K: Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its related extracellular matrix degrading enzymes in the endometrium during estrous cycle and early gestation in cattle. Reprod Biol Endocrinol. 8:602010. View Article : Google Scholar : PubMed/NCBI
36	Su MT, Tsai PY, Tsai HL, Chen YC and Kuo PL: MiR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9. Biofactors. 43:210–219. 2017. View Article : Google Scholar : PubMed/NCBI
37	Isaka K, Usuda S, Ito H, Sagawa Y, Nakamura H, Nishi H, Suzuki Y, Li YF and Takayama M: Expression and activity of matrix metalloproteinase 2 and 9 in human trophoblasts. Placenta. 24:53–64. 2003. View Article : Google Scholar : PubMed/NCBI
38	Kunes P, Holubcova Z, Kolackova M and Krejsek J: Pentraxin 3(PTX 3): An endogenous modulator of the inflammatory response. Mediators Inflamm. 2012:9205172012. View Article : Google Scholar : PubMed/NCBI
39	Equils O, Kellogg C, McGregor J, Gravett M, Neal-Perry G and Gabay C: The role of the IL-1 system in pregnancy and the use of IL-1 system markers to identify women at risk for pregnancy complications†. Biol Reprod. 103:684–694. 2020. View Article : Google Scholar : PubMed/NCBI
40	Takamura S, Takahashi A, Inoue Y and Teraki Y: Effects of tumor necrosis factor-alpha, interleukin-23 and interleukin-17A inhibitors on bodyweight and body mass index in patients with psoriasis. J Dermatol. 45:1130–1134. 2018. View Article : Google Scholar : PubMed/NCBI
41	Kocyigit Y, Atamer Y, Atamer A, Tuzcu A and Akkus Z: Changes in serum levels of leptin, cytokines and lipoprotein in pre-eclamptic and normotensive pregnant women. Gynecol Endocrinol. 19:267–273. 2004. View Article : Google Scholar : PubMed/NCBI
42	Luppi P and Deloia JA: Monocytes of preeclamptic women spontaneously synthesize pro-inflammatory cytokines. Clin Immunol. 118:268–275. 2006. View Article : Google Scholar : PubMed/NCBI
43	Alanbay I, Coksuer H, Ercan CM, Ustun Y, Pala G, Karasahin KE, Ozturk O, Kurt I and Baser I: Chitotriosidase, interleukin-1 beta and tumor necrosis factor alpha levels in mild preeclampsia. Arch Gynecol Obstet. 285:1505–1511. 2012. View Article : Google Scholar : PubMed/NCBI
44	Hannum CH, Wilcox CJ, Arend WP, Joslin FG, Dripps DJ, Heimdal PL, Armes LG, Sommer A, Eisenberg SP and Thompson RC: Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 343:336–340. 1990. View Article : Google Scholar : PubMed/NCBI
45	Powers NE, Swartzwelter B, Marchetti C, de Graaf DM, Lerchner A, Schlapschy M, Datar R, Binder U, Edwards CK III, Skerra A and Dinarello CA: PASylation of IL-1 receptor antagonist (IL-1Ra) retains IL-1 blockade and extends its duration in mouse urate crystal-induced peritonitis. J Biol Chem. 295:868–882. 2020. View Article : Google Scholar : PubMed/NCBI