Gebelik sırasında nazal mukozada NFκb ve MUC5AC ekspresyon düzeylerinin değişimi

Year 2020, , 771 - 774, 01.09.2020

Burak Ülkümen , Burcu Artunc-ulkumen , Muhammet Burak Batir , Sırrı Çam

https://doi.org/10.28982/josam.789704

Abstract

Amaç: Üst solunum yolunun kronik enflamatuar hastalıklarının gebelikteki seyri konusunda çok sınırlı bilgi mevcuttur. Bu çalışmada, NFκb ve MUC5AC ile ilgili olarak hamilelik sırasında nazal mukozadaki biyomoleküler değişiklikleri ortaya çıkarmaya çalıştık. Bu sayede, gebeliğe bağlı burun rahatsızlıkları için yeni tedavi stratejileri önerme fırsatımız olabilir.
Yöntemler: Sıçanlar üzerinde yapılan bu çalışma, Deney Hayvanları Araştırma ve Uygulama Merkezinde yapılmıştır. Otuz yetişkin Wister albino dişi sıçan, bir kontrol grubu ve bir hamile grubu olarak ayrıldı. Serum estradiole (E2) ve progesteron (PG) düzeyleri ELISA ile değerlendirildi. NFκb ve MUC5AC'nin nazal ekspresyonu, polimeraz zincir reaksiyon testi ile analiz edildi. İstatistiksel analiz, NFkb ve MUC5AC ekspresyonunun grup bazında karşılaştırılması ile yapıldı. Ayrıca E2 ve PG seviyelerinin bu moleküller üzerindeki etkisi de araştırıldı.
Bulgular: Gebe sıçanlarda NFκb anlamlı olarak düşük (P=0,015) bulunurken MUC5AC anlamlı derecede yüksek bulundu (P=0.029). Serum PG ve NF-κB ekspresyonu arasında istatistiksel olarak anlamlı negatif korelasyon (P=0,027), progesteron ile MUC5AC ekspresyonu arasında ise pozitif korelasyon (P=0,017) bulundu. Ek olarak, estradiol ve MUC5AC arasında pozitif korelasyon tespit ettik (P=0.017).
Sonuçlar: Bu çalışmada, sıçan nazal mukozasında NFκb ve MUC5AC'nin fizyolojik ekspresyonu ilk kez PCR ile gösterilmiştir. E’ ve PG’nin bu biyomoleküllerin ekspresyonu üzerindeki etkisi de gebelik bağlamında ortaya konmuştur. Bu bulgular, üst solunum yolunun gestasyonel enflamatuar değişikliklerini açıklama potansiyeline sahiptir.

Keywords

Gebelik, Bağışıklık, NFκb, MUC5AC, Nazal mukoza

Supporting Institution

Manisa Celal Bayar Üniversitesi

Project Number

2014-131

Change in expression of NFκb and MUC5AC in nasal mucosa during pregnancy

Abstract

Aim: There is very limited information concerning gestational course of chronic inflammatory diseases of the upper airway. In the current study, we tried to reveal biomolecular changes in the nasal mucosa during pregnancy regarding NFκb and MUC5AC. This way, we may have the opportunity to suggest new treatment strategies for pregnancy induced nasal disorders.
Methods: Thirty adult female rats were separated into pregnant and control groups. Serum estradiole (E2) and progesterone (PG) levels were evaluated by ELISA. Nasal expression of NFκb and MUC5AC were analyzed by polymerase chain reaction testing. Relative expression of NFκb and MUC5AC was compared between two groups. In addition, the influences of PG and E2 levels on NFκb and MUC5AC were determined.
Results: NFκb was significantly low (P=0.015), while MUC5AC was significantly high in pregnant rats (P=0.029). Serum PG had a significantly negative effect on NF-κB expression (P=0.027) and a significantly positive effect on MUC5AC expression (P=0.017). There was a positive correlation between estradiol and MUC5AC (P=0.017).
Conclusions: In the current study, the physiological expression of NFκb and MUC5AC was shown for the first time by PCR in rat nasal mucosa. The effect of PG and E2 on the expression of these biomolecules in the context of pregnancy was also revealed. These findings have the potential to elucidate gestational inflammatory alterations in the upper airway.

Keywords

pregnancy, immunity, NFκb, MUC5AC, nasal mucosa

Project Number

2014-131

References

• 1. Sakowicz A. The role of NFκB in the three stages of pregnancy – implantation, maintenance, and labour: a review article. BJOG. 2018;125(11):1379-87. doi: 10.1111/1471-0528.15172.
• 2. Dale E, Davis M, Faustman DL. A role for transcription factor NF-kappaB in autoimmunity: possible interactions of genes, sex, and the immune response. Adv Physiol Educ. 2006;30(4):152-8. Review.
• 3. Santos RS, de Fatima LA, Frank AP, Carneiro EM, Clegg DJ. The effects of 17 alpha-estradiol to inhibit inflammation in vitro. Biol Sex Differ. 2017;8(1):30. doi: 10.1186/s13293-017-0151-9.
• 4. Fernandez-Valdivia R, Lydon JP. From the ranks of mammary progesterone mediators, RANKL takes the spotlight. Mol Cell Endocrinol. 2012;357(1-2):91-100. doi: 10.1016/j.mce.2011.09.030.
• 5. Garside H, Stevens A, Farrow S, Normand C, Houle B, Berry A, et al. Glucocorticoid ligands specify different interactions with NF-kappaB by allosteric effects on the glucocorticoid receptor DNA binding domain. J Biol Chem. 2004;279(48):50050-9.
• 6. Ulkumen B, Artunc Ulkumen B, Batir MB, Pala HG, Vatansever S, Cam S. Impact of Pregnancy and Glucocorticoid Treatment on NF-κB and MUC5AC in Mucosa of Rat Larynx. J Voice. 2019 Dec 2. pii: S0892-1997(19)30470-9. doi: 10.1016/j.jvoice.2019.11.008.
• 7. Wang W, Zheng M. Mucin 5 subtype AC expression and upregulation in the nasal mucosa of allergic rhinitis rats. Otolaryngol Head Neck Surg. 2012;147(6):1012-9.
• 8. Tam A, Wadsworth S, Dorscheid D, Man SF, Sin DD. Estradiol increases mucus synthesis in bronchial epithelial cells. PLoS One. 2014;9(6):e100633. doi: 10.1371/journal.pone.0100633.
• 9. Agematsu Y, Ikadai H, Amao H. Early detection of pregnancy of the rat. Jikken Dobutsu. 1983;32:209-12. doi: 10.1538/expanim1978.32.4_209
• 10. Lohmiller JJ, Swing SP. Reproduction and Breeding. In: Suckow MA., Weisbroth SH, Franklin CL, editors. The laboratory rat. Boston, United States: Elsevier; 2006. p. 147-165.
• 11. Ulkumen B, Artunc Ulkumen B, Batir MB, Pala HG, Vatansever S, Cam S. (2019). Impact of Pregnancy and Glucocorticoid Treatment on NF-κB and MUC5AC in Mucosa of Rat Larynx. Journal of Voice, doi: 10.1016/j.jvoice.2019.11.008
• 12. Witlin AG, Li ZY, Wimalawansa SJ, Grady JJ, Grafe MR, Yallampalli C. Placental and fetal growth and development in late rat gestation is dependent on adrenomedullin. Biol Reprod. 2002; 67:1025-31.
• 13. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
• 14. Başer Açıkgöz R. Spontaneous vaginal delivery after a pregnancy complicated with Guillain-Barré syndrome. J Surg Med. 2018;2(2):143-4.
• 15. ACOG Practice Bulletin; Asthma in Pregnancy; Clinical Management Guidelines For Obstetrician-Gynecologists; VOL. 111, NO. 2, PART 1, FEBRUARY 2008.
• 16. Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett WS, Leaderer BP. Asthma symptoms, severity, and drug therapy: a prospective study of effects on 2205 pregnancies. Obstet Gynecol 2003;102:739–52.
• 17. McCracken SA, Gallery E, Morris JM. Pregnancy‐specific down‐regulation of NF‐kappa B expression in T cells in humans is essential for the maintenance of the cytokine profile required for pregnancy success. J Immunol 2004;172:4583–91.
• 18. Thibeault SL, Rees L, Pazmany L, Birchall MA. At the crossroads: mucosal immunology of the larynx. Mucosal Immunol. 2009;2(2):122-8.
• 19. Tacchi, L. et al. Nasal immunity is an ancient arm of the mucosal immune system of vertebrates. Nat Commun. 2014;5:5205. doi: 10.1038/ncomms6205.
• 20. Armistead B, Kadam L, Drewlo S, Kohan-Ghadr HR. The Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight. Int J Mol Sci. 2020;21(5):1775. doi: 10.3390/ijms21051775
• 21. Shah NM, Lai PF, Imami N, Johnson MR. Progesterone-Related Immune Modulation of Pregnancy and Labor. Front Endocrinol (Lausanne). 2019;10:198.
• 22. Stice JP, Mbai FN, Chen L, Knowlton AA. Rapid Activation of Nuclear Factor-κB by 17β-Estradiol and Selective Estrogen Receptor Modulators: Pathways Mediating Cellular Protection. Shock. 2012;38(2):128–36.
• 23. Simoncini T, Maffei S, Basta G, Barsacchi G, Genazzani AR, Liao JK, et al. Estrogens and Glucocorticoids Inhibit Endothelial Vascular Cell Adhesion Molecule-1 Expression by Different Transcriptional Mechanisms. Circulation Research. 2000 July;87(1):19–25.
• 24. Lange C, Fernandez J, Shim D, Spurr-Michaud S, Tisdale A, Gipson IK. Mucin gene expression is not regulated by estrogen and/or progesterone in the ocular surface epithelia of mice. Exp Eye Res. 2003;77(1):59‐68.
• 25. McNeer RR, Carraway CA, Fregien NL, Carraway KL. Characterization of the expression and steroid hormone control of sialomucin complex in the rat uterus: implications for uterine receptivity. J Cell Physiol. 1998;176(1):110-9. doi: 10.1002/(SICI)1097-4652(199807)176:1<110::AID-JCP13>3.0.CO;2-B