Endometriotik dokularda interlökin-6 ve tümör nekroz faktör alfa ekspresyonu: bir immünohistokimyasal çalışma
Yıl 2020,
Cilt: 45 Sayı: 3, 1115 - 1125, 30.09.2020
Nimet Furucu
Leman Sencar
,
M.turan Çetin
,
İbrahim Ferhat Ürünsak
Derya Gümürdülü
Sait Polat
Öz
Amaç: Bu çalışmada, insanda normal endometriyum ve endometriyotik dokularda Tümör nekroz faktör-α (TNF-α) ve Interlökin-6 (IL-6) ekspresyonlarının immünohistokimyasal yöntemler ile araştırılması amaçlandı.
Gereç ve Yöntem: Çalışmada incelenen doku kesitleri, 20-40 yaşları arasındaki 24 kadından alınan ektopik endometriyum doku biyopsilerinden elde edildi. Ayrıca herhangi bir endometriyal fonksiyon bozukluğu bulunmayan, ancak diletasyon veya küretaj nedeniyle, 10 hastadan elde edilen endometriyum dokularından alınan kesitler de kontrol grubu olarak değerlendirildi. Işık mikroskobik ve immünohistokimyasal yöntemler ile hazırlanan doku kesitleri, ışık mikroskopta incelendi.
Bulgular: TNF-α ve IL-6 ekspresyonunun kontrol grubunda yüzey ve bez epitelinde zayıftan orta dereceye kadar değişen düzeylerde olduğu gözlendi. Buna karşın stromal hücrelerde belirgin bir boyanmaya rastlanmadı. TNF-α ve IL-6'nın endometriyotik dokulardaki immünreaktivitesinin kontrol endometriyum ile karşılaştırıldığında, epitel hücreleri ile stromal hücreler ve makrofajlarda belirgin olarak artış gösterdiği bulundu. TNF-α ve IL-6 ekspresyonlarının her ikisi de ektopik endometriyal dokuda, güçlü olarak eksprese olmuştur.
Sonuç: TNF-α ve IL-6’nın endometriyozis oluşumu ve patogenezinde rol alan önemli sitokinler oldukları kanaatine varıldı.
Destekleyen Kurum
Ç.Ü Bilimsel Araştırma Projeleri Birimi
Kaynakça
- 1. Rogers K. The reproductive system, The human body. 1st ed, New York: Britannica Educational Publishing. 2011: 42-7.
- 2. Ross MH, Pawlina W. Histology: A text and atlas. 6th ed. Philadelphia: Lippincott Williams & Wilkins. 2011: 848 – 53.
- 3. Tagashira Y, Taniguchi F, Harada T. Interleukin-10 attenuates TNF-a–induced interleukin-6 production in endometriotic stromal cells. Fertility and Sterility. 2009; 91(5):2185-92.
- 4. Salmassi A, Acil Y, Schmutzler A G, Koch K, Jonat W, Mettler L. Differential interleukin-6 messenger ribonucleic acid expression and its distribution pattern in eutopic and ectopic endometrium. Fertility and Sterility. 2008; 89(3):1578-84.
- 5. Hadisaputra W. Clinical signs, symptoms and serum level of interleukin-6 and tumor necrosis factor in women with or without endometriosis. Asian Pacific Journal of Reproduction. 2013; 2(2): 142-5.
- 6. Wickiewicz D, Chrobak A, Gmyrek G B, Halbersztadt A, Gabrys´ M S, Goluda M, Chełmon´ska- Soyta A. Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis. Archives of Gynecology and Obstetrics. 2013; 288(4): 805-14.
- 7. Ponce C, Torres M, Galleguillos C, Sovino H, Boric A, Fuentes A, Johnson C. Nuclear factor KB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis. Reproduction. 2009; 137: 727–37.
- 8. Baştu E, Mutlu M F, Yaşa C, Attar N E. Endometriyozis ve İmmünoloji. Turkish Journal of Immunology. 2013; 1(2):54-62.
- 9. Giudice LC. Endometriosis. The New England Journal of Medicine, 2004; 364: 1789–99.
- 10. Wu MY, Ho HN. The Role of Cytokines in Endometriosis. Amerıcan Journal of Reproductıve Immunology. 2003; 49: 285–96.
- 11. Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson D. Agarwal A. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Human Reproduction. 2002;17: 426-31.
- 12. Haider S, Knöfler M. Human tumor necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta. 2009; 30: 111-23.
- 13. Ryan IP, Tseng JF, Schriock ED, Khorram O, Landers DV, Taylor RN. Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril. 1995; 63(4):929-32.
- 14. Punnonen J, Teisala K, Ranta H, Bennett B, Punnonen R. Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis. Am J Obstet Gynecol. 1996; 174(5):1522-6.
- 15. Oosterlynck D J, Meuleman C, Waer M, Koninckx P R. Transforming Growth Factor-β activity is increased in peritoneal fluid from women with endometriosis. Obstet Gynecol. 1994;83: 287-92.
- 16. McLaren J, Prentice A, Charnock-Jones DS, Millican SA, Müller KH, Sharkey AM, Smith SK. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest. 1996; 98(2):482-9.
- 17. Harada T, Yoshioka H, Yoshida S, Iwabe T, Onohara Y, Tanikawa M et al. Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis. Am J Obstet Gynecol. 1997;176(3):593-7.
- 18. Ilie I, Ilie R. Cytokines and endometriosis - the role of immunological alterations. Biotechnology, Molecular Biology and Nanomedicine. 2013; 1(2):8-19.
- 19. Vigano P, Parazzini F, Somigliana E, Vercellini P. Endometriosis: epidemiology and aetiological factors. Elsevier. 2004; 18(2): 177–200.
- 20. Sourial S, Tempest N, Hapangama D K. Theories on the Pathogenesis of Endometriosis. International Journal of Reproductive Medicine. 2014; 2014:1-9.
- 21. Boric MA, Torres M, Pinto C, Pino M, Hidalgo P, Gabler F, et al. TNF system in eutopic endometrium from women with endometriosis. Open Journal of Obstetrics and Gynecology. 2013; 3: 271-78.
- 22. Li J, Chen Y, Wei S, Wu H, Liu C, Huang Q et al. Tumor necrosis factor and interleukin-6 gene polymorphisms and endometriosis risk in Asians: a systematic review and meta-analysis. Ann Hum Genet. 2014; 78(2):104-16.
- 23. Fakih H, Baggett B, Holtz G, Tsang KY, Lee JC, Williamson HO. Interleukin-1: A possible role in the infertility associated with endometriosis. Fertil Steril. 1987; 47(2):213-7.
- 24. Ryan IP, Tseng JF, Schriock ED, Khorram O, Landers DV, Taylor RN. Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril. 1995;63(4):929-32.
- 25. Ulukus M, Ulukus E.C, Tavmergen Goker E.N, Tavmergen E, Zheng W, Arici A. Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis. Fertil Steril. 2009; 91:687–93.
- 26. Punnonen J, Teisala K, Ranta H, Bennett B, Punnonen R. Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis. Am J Obstet Gynecol. 1996; 174(5):1522-6.
- 27. Haider S, Knöfler M. Human tumor necrosois factor: physiological and pathological roles in placenta and endometrium. Placenta. 2009; 30:111-23.
- 28. Kock A, Schwarz T, Kirnbauer R, Urbanski A, Perry P, Ansel JC et al. Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. J. Exp Med. 1990;172: 1609-14.
- 29. Von Wolff M, Classen-Linke I, Heid D, Krusche CA, Beier-Hellwig K, Karl C et al. Tumour necrosis factor-alpha (TNF-alpha) in human endometrium and uterine secretion: an evaluation by immunohistochemistry, ELISA and semiquantitative RT-PCR. Molecular Human Reproduction. 1999;5 (2): 146–52.
- 30. Kalb A, Bluethmann H, Moore MW, Lesslauer W. Tumor necrosis factor receptors (Tnfr) in mouse fibroblasts deficient in Tnfr1 or Tnfr2 are signaling competent and activate the mitogen-activated protein kinase pathway with differential kinetics. The Journal of biological chemistry. 1996; 271:28097-104.
- 31. Fajardo LF, Kwan HH, Kowalski J, Prionas SD, Allison AC. Dual role of tumor necrosis factor-alpha in angiogenesis. The American journal of pathology. 1992;140:539-44.
- 32. Taketani Y, Kuo TM, Mizuno M. Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis. American journal of obstetrics and gynecology. 1992;167:265-70.
- 33. Bullimore D. Endometriosis is sustained by tumour necrosis factor alpha. Medical Hypotheses. 2003; 60: 84-8.
- 34. Philippeaux MM, Piguet PF. Expression of tumor necrosis factor alpha and its mRNA in the endometrial mucosa during the menstrual cycle. Am J Pathol. 1993; 143:480-6.
- 35. Hunt JS, Chen HL, Hu XL, Tabibzadeh S. Tumor necrosis factor alpha messenger ribonucleic asid and protein in human endometrium. Biol Reprod. 1992; 47:141-7.
- 36. Dmowski W, Braun D. Immunology of endometriosis. Best Practice Clinical Obstetrics and Gynecology. 2004; 18:245-63.
- 37. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011; 1813(5):878-88.
Expression of interleukin 6 and tumor necrosis factor alpha in endometriotic tissues: an immunohistochemical study
Yıl 2020,
Cilt: 45 Sayı: 3, 1115 - 1125, 30.09.2020
Nimet Furucu
Leman Sencar
,
M.turan Çetin
,
İbrahim Ferhat Ürünsak
Derya Gümürdülü
Sait Polat
Öz
Purpose: The aim of this study is to investigate Tumor necrosis factor alpha (TNF-α) and Interleukin 6 (IL-6) expressions in normal and endometriotic human tissue using immunohistochemical methods.
Materials and Methods: This study examined tissue sections obtained from the tissue biopsies of ectopic endometrium taken from 24 women between the ages of 20 to 40 years. Additionally, the tissue sections taken from the normal endometrium obtained from 10 patients without any endometrial dysfunction due to dilation or curettage were also evaluated, as the control group. Tissue sections prepared by light microscopic and immunohistochemical methods were examined under a light microscope.
Results: In the control group TNF-α and IL-6 expressions were identified at varying levels, from weak to moderate, in surface and glandular epithelium; however, there was no evidence of a significant staining in the stromal cells. It is found that TNF-α and IL-6 immunoreactivity in the endometriotic tissues were significantly increased in the epithelial cells, stromal cells and macrophages compared to the control endometrium. Expressions of TNF-α and IL-6 were both strong in the ectopic endometrial tissues.
Conclusion: We conclude that TNF-α and IL-6 are important cytokines involved in the pathogenesis of the endometriosis.
Kaynakça
- 1. Rogers K. The reproductive system, The human body. 1st ed, New York: Britannica Educational Publishing. 2011: 42-7.
- 2. Ross MH, Pawlina W. Histology: A text and atlas. 6th ed. Philadelphia: Lippincott Williams & Wilkins. 2011: 848 – 53.
- 3. Tagashira Y, Taniguchi F, Harada T. Interleukin-10 attenuates TNF-a–induced interleukin-6 production in endometriotic stromal cells. Fertility and Sterility. 2009; 91(5):2185-92.
- 4. Salmassi A, Acil Y, Schmutzler A G, Koch K, Jonat W, Mettler L. Differential interleukin-6 messenger ribonucleic acid expression and its distribution pattern in eutopic and ectopic endometrium. Fertility and Sterility. 2008; 89(3):1578-84.
- 5. Hadisaputra W. Clinical signs, symptoms and serum level of interleukin-6 and tumor necrosis factor in women with or without endometriosis. Asian Pacific Journal of Reproduction. 2013; 2(2): 142-5.
- 6. Wickiewicz D, Chrobak A, Gmyrek G B, Halbersztadt A, Gabrys´ M S, Goluda M, Chełmon´ska- Soyta A. Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis. Archives of Gynecology and Obstetrics. 2013; 288(4): 805-14.
- 7. Ponce C, Torres M, Galleguillos C, Sovino H, Boric A, Fuentes A, Johnson C. Nuclear factor KB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis. Reproduction. 2009; 137: 727–37.
- 8. Baştu E, Mutlu M F, Yaşa C, Attar N E. Endometriyozis ve İmmünoloji. Turkish Journal of Immunology. 2013; 1(2):54-62.
- 9. Giudice LC. Endometriosis. The New England Journal of Medicine, 2004; 364: 1789–99.
- 10. Wu MY, Ho HN. The Role of Cytokines in Endometriosis. Amerıcan Journal of Reproductıve Immunology. 2003; 49: 285–96.
- 11. Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson D. Agarwal A. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Human Reproduction. 2002;17: 426-31.
- 12. Haider S, Knöfler M. Human tumor necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta. 2009; 30: 111-23.
- 13. Ryan IP, Tseng JF, Schriock ED, Khorram O, Landers DV, Taylor RN. Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril. 1995; 63(4):929-32.
- 14. Punnonen J, Teisala K, Ranta H, Bennett B, Punnonen R. Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis. Am J Obstet Gynecol. 1996; 174(5):1522-6.
- 15. Oosterlynck D J, Meuleman C, Waer M, Koninckx P R. Transforming Growth Factor-β activity is increased in peritoneal fluid from women with endometriosis. Obstet Gynecol. 1994;83: 287-92.
- 16. McLaren J, Prentice A, Charnock-Jones DS, Millican SA, Müller KH, Sharkey AM, Smith SK. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest. 1996; 98(2):482-9.
- 17. Harada T, Yoshioka H, Yoshida S, Iwabe T, Onohara Y, Tanikawa M et al. Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis. Am J Obstet Gynecol. 1997;176(3):593-7.
- 18. Ilie I, Ilie R. Cytokines and endometriosis - the role of immunological alterations. Biotechnology, Molecular Biology and Nanomedicine. 2013; 1(2):8-19.
- 19. Vigano P, Parazzini F, Somigliana E, Vercellini P. Endometriosis: epidemiology and aetiological factors. Elsevier. 2004; 18(2): 177–200.
- 20. Sourial S, Tempest N, Hapangama D K. Theories on the Pathogenesis of Endometriosis. International Journal of Reproductive Medicine. 2014; 2014:1-9.
- 21. Boric MA, Torres M, Pinto C, Pino M, Hidalgo P, Gabler F, et al. TNF system in eutopic endometrium from women with endometriosis. Open Journal of Obstetrics and Gynecology. 2013; 3: 271-78.
- 22. Li J, Chen Y, Wei S, Wu H, Liu C, Huang Q et al. Tumor necrosis factor and interleukin-6 gene polymorphisms and endometriosis risk in Asians: a systematic review and meta-analysis. Ann Hum Genet. 2014; 78(2):104-16.
- 23. Fakih H, Baggett B, Holtz G, Tsang KY, Lee JC, Williamson HO. Interleukin-1: A possible role in the infertility associated with endometriosis. Fertil Steril. 1987; 47(2):213-7.
- 24. Ryan IP, Tseng JF, Schriock ED, Khorram O, Landers DV, Taylor RN. Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril. 1995;63(4):929-32.
- 25. Ulukus M, Ulukus E.C, Tavmergen Goker E.N, Tavmergen E, Zheng W, Arici A. Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis. Fertil Steril. 2009; 91:687–93.
- 26. Punnonen J, Teisala K, Ranta H, Bennett B, Punnonen R. Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis. Am J Obstet Gynecol. 1996; 174(5):1522-6.
- 27. Haider S, Knöfler M. Human tumor necrosois factor: physiological and pathological roles in placenta and endometrium. Placenta. 2009; 30:111-23.
- 28. Kock A, Schwarz T, Kirnbauer R, Urbanski A, Perry P, Ansel JC et al. Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. J. Exp Med. 1990;172: 1609-14.
- 29. Von Wolff M, Classen-Linke I, Heid D, Krusche CA, Beier-Hellwig K, Karl C et al. Tumour necrosis factor-alpha (TNF-alpha) in human endometrium and uterine secretion: an evaluation by immunohistochemistry, ELISA and semiquantitative RT-PCR. Molecular Human Reproduction. 1999;5 (2): 146–52.
- 30. Kalb A, Bluethmann H, Moore MW, Lesslauer W. Tumor necrosis factor receptors (Tnfr) in mouse fibroblasts deficient in Tnfr1 or Tnfr2 are signaling competent and activate the mitogen-activated protein kinase pathway with differential kinetics. The Journal of biological chemistry. 1996; 271:28097-104.
- 31. Fajardo LF, Kwan HH, Kowalski J, Prionas SD, Allison AC. Dual role of tumor necrosis factor-alpha in angiogenesis. The American journal of pathology. 1992;140:539-44.
- 32. Taketani Y, Kuo TM, Mizuno M. Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis. American journal of obstetrics and gynecology. 1992;167:265-70.
- 33. Bullimore D. Endometriosis is sustained by tumour necrosis factor alpha. Medical Hypotheses. 2003; 60: 84-8.
- 34. Philippeaux MM, Piguet PF. Expression of tumor necrosis factor alpha and its mRNA in the endometrial mucosa during the menstrual cycle. Am J Pathol. 1993; 143:480-6.
- 35. Hunt JS, Chen HL, Hu XL, Tabibzadeh S. Tumor necrosis factor alpha messenger ribonucleic asid and protein in human endometrium. Biol Reprod. 1992; 47:141-7.
- 36. Dmowski W, Braun D. Immunology of endometriosis. Best Practice Clinical Obstetrics and Gynecology. 2004; 18:245-63.
- 37. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011; 1813(5):878-88.