Role of nuclear factor kappa beta, tumor necrosis factor α, and cyclooxygenase-2 in preterm labor
DOI:
https://doi.org/10.13181/mji.v23i4.1005Keywords:
COX-2, NF-κB, TNFα, preterm laborAbstract
Background: The pathway of tumor necrosis factor alpha (TNFα), nuclear factor kappa beta (NF-κB), and cyclooxygenase-2 (COX-2) activation in releasing prostaglandins is suggested to be crucial for initiating labor in the pathogenesis of preterm labor. The aim of the study was to know whether there were mean differences of NF-κB, TNFα, and COX-2 expressions between preterm and term labor and also to know the correlation among them in preterm labor.
Methods: A case-control study was performed from May 2013 to February 2014 in Arifin Achmad Hospital, Pekanbaru. There were 30 subjects with preterm labor as cases and 30 with normal labor as controls. All subjects had singleton gestation with maximum parity was three, age limit of 35 year-old, and spontaneous labor in both groups. Placental tissue was collected from all subjects and evaluated with hematoxylin eosin staining. The expressions of TNFα, NF-κB, and COX-2 in the tissue were assessed with immunohistochemical staining by counting the percentage of smeared cells by two experts. The expressions of TNFα, NF-κB, and COX-2 between case and control were compared using t-test and the correlation was analyzed with Pearson correlation coefficient.
Results: Mean (SD) of expressions of TNFα (93.05% [12.68] vs 49.11% [27.33]), NF-κB (42.46% [27.29] vs 13.66% [17.77]), and COX-2 (88.75% [10.86] vs 46% [30.36]) were significantly higher in the preterm labor compared to term labor (p = 0.001). There was significant correlation between TNFα and NF-κB expression (r = 0.385; p = 0.036) and no correlation was found between NF-κB and COX-2 (p = 0.982) in preterm labor.
Conclusion: High expressions of TNFα, NF-κB, and COX-2 in preterm labor showed to contribute in the onset of preterm labor. High TNFα may suggest that infection was a leading cause of preterm labor. This is supported with an increase in NF-κB activation will increase COX-2 and subsequently prostaglandins that result in premature labor.
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Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012;379(9832):2162-72. http://dx.doi.org/10.1016/S0140-6736(12)60820-4
Usman I, Effendi JS. Tinjauan kasus persalinan premature di RSHS tahun 1998-2000. In, PIT POGI XII. Palembang; 2001. Indonesian.
WHO. WHO: recommended definitions, terminology and format for statistical tables related to the perinatal period and use of a new certificate for cause of perinatal deaths. Modifications recommended by FIGO as amended October 14, 1976. Acta Obstet Gynecol Scand. 1977;56(3):247-53.
Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75-84. http://dx.doi.org/10.1016/S0140-6736(08)60074-4
Koucký M, Germanová A, Hájek Z, Pa?ízek A, Kalousová M, Kopecký P. Pathophysiology of preterm labour. Prague Med Rep 2009;110(1):13-24.
Simmons LE, Rubens CE, Darmstadt GL, Gravett MG. Preventing preterm birth and neonatal mortality: exploring the epidemiology, causes and interventions. Semin Perinatol. 2010;34(6):408-15. http://dx.doi.org/10.1053/j.semperi.2010.09.005
Collins JJ, Usip S, McCarson KE, Papka RE. Sensory nerves and neuropeptides in uterine cervical ripening. Peptides. 2002;23(1):167-83. http://dx.doi.org/10.1016/S0196-9781(01)00593-9
Lindström TM, Bennett PR. The role of nuclear factor kappa B in human labour. Reproduction. 2005;130(5):569-81. http://dx.doi.org/10.1530/rep.1.00197
Palliser HK, Hirst JJ, Ooi GT, Rice GE, Dellios NL, Escalona RM, et al. Prostaglandin E and F receptor expressionand myometrial sensitivity at labor onset in the sheep. Biol Reprod. 2005;72(4):937-43. http://dx.doi.org/10.1095/biolreprod.104.035311
Lappas M, Yee K, Permezel M, Rice GE. Lipopolysaccharide and TNF-a activate the nuclear factor kappa B pathway in the human placental JEG-3 cells. Placenta. 2006; 27(6-7):568-75. http://dx.doi.org/10.1016/j.placenta.2005.06.003
Burdon C, Mann C, Cindrova-Davies T, Ferguson-Smith AC, Burton GJ. Oxidative stress and the induction of cyclooxygenase enzymes and apoptosis in the murine placenta. Placenta. 2007;28(7):724-33. http://dx.doi.org/10.1016/j.placenta.2006.12.001
Cindrova-Davies T, Yung HW, Johns J, Spasic-Boskovic O, Korolchuk S, Jauniaux E, et al. Oxidative stress, gene expression, and protein changes induced in the human placenta during labor. Am J Pathol. 2007;171(4):1168-79. http://dx.doi.org/10.2353/ajpath.2007.070528
Lockwood CJ. Stress-associated preterm delivery: the role of corticotrophin-releasing hormone. Am J Obstet Gynecol. 1999; 180(1 Pt 3):S264-6. http://dx.doi.org/10.1016/S0002-9378(99)70713-1
Ackerman WE 4th, Zhang XL, Rovin BH, Kniss DA. Modulation of cytokine-induced cyclooxygenase 2 expression by PPARG ligands through NF kappa B signal disruption in human WISH and amnion cells. Biol Reprod. 2005;73(3):527-35. http://dx.doi.org/10.1095/biolreprod.104.039032
Christman JW, Sadikot RT, Blackwell TS. The role of nuclear factor kappa-B in lung disease. Chest. 2000;117(5):1482-7. http://dx.doi.org/10.1378/chest.117.5.1482
Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol. 2006;72(11):1605-21. http://dx.doi.org/10.1016/j.bcp.2006.06.029
Yamamoto Y, Gaynor RB. Potential therapeutic inhibition of NF-kB pathway in the treatment of inflammation and cancer. J Clin Invest. 2001;107(2):135-42. http://dx.doi.org/10.1172/JCI11914
Condon JC, Hardy DB, Kovaric K, Mendelson CR. Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-kappaB may contribute to the onset of labor through inhibition of PR function. Mol Endocrinol. 2006;20(4):764-75. http://dx.doi.org/10.1210/me.2005-0242
Chen YH, Zhao M, Chen X, Zhang Y, Wang H, Huang YY, et al. Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect. J Immunol. 2012;189(1):454-63. http://dx.doi.org/10.4049/jimmunol.1103579
Orlando RA, Gonzales AM, Hunsaker LA, Franco CR, Royer RE, Vander Jagt DL, et al. Inhibition of nuclear factor kB activation and cyclooxygenase-2 expression by aqueous extracts of Hispanic medicinal herbs. J Med Food. 2010;13(4):888-95. http://dx.doi.org/10.1089/jmf.2009.1128
Zhao M, Chen YH, Dong XT, Zhou J, Chen X, Wang H, et al. Folic acid protects against lipopolysaccharide-induced preterm delivery and intrauterine growth restriction through its anti-inflammatory effect in mice. PLoS ONE 2013;8(12):e82713. http://dx.doi.org/10.1371/journal.pone.0082713
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