Research Article
BibTex RIS Cite

Ülseratif Kolitli Hastalarda Netrin-1 Düzeyinin Klinik ve Hastalık Aktivitesini Değerlendirmedeki Rolü ve TNF-alfa, IL-6 ile İlişkisi

Year 2022, Volume: 7 Issue: 2, 247 - 252, 01.06.2022
https://doi.org/10.26453/otjhs.931360

Abstract

Amaç: Bu çalışmada Ülseratif Kolit (ÜK)'de netrin-1 düzeylerinin hastalığın klinik aktivitesindeki önemi ve diğer proinflamatuar sitokinlerden IL-6 ve TNF-alfa ile ilişkisini araştırdık.
Materyal ve Metot: Bu çalışma bir vaka control çalışması olup çalışmaya ÜK'li 67 hasta (36'sı aktivasyonlu, 31'i remisyonda) ve 50 sağlıklı kontrol dahil edildi. ÜK hastaları; "Truelove Witts klinik aktivite indeksi"ne göre hafif aktivasyon (n=21), orta aktivasyon (n=6) ve şiddetli aktivasyon (n=9) gruplarına ayrıldı. Asemptomatik olan 31 hasta Montreal sınıflandırılmasına göre remisyonda kabul edildi. Plazma örneklerindeki netrin-1, IL-6 ve TNF-alfa ölçümleri, ELİSA test kiti kullanılarak yapıldı.
Bulgular: Hasta grubu ile kontrol grubu arasında; netrin-1, IL-6 ve TNF-alfa düzeyleri arasında istatistiksel olarak anlamlı bir fark vardı (p<0,05). Şiddetli aktivasyon grubunda plazma netrin-1 düzeyi hafif şiddetli grup, remisyon grubu ve kontrol grubuna göre istatistiksel olarak daha yüksekti (p<0,05). ÜK grupları arasında TNF-alfa düzeyi istatistiksel olarak anlamlı bulunmazken (p>0,05), IL-6 düzeyi ise gruplar arasında anlamlı bulundu (p<0,05). Ayrıca netrin-1 ile IL-6 arasında pozitif yönde bir korelasyon saptanırken, netrin-1 ile TNF-alfa arasında korelasyon saptanmadı.
Sonuç: Çalışmamız; plazma netrin-1 düzeylerinin, TNF-alfa ve IL-6 gibi proinflamatuar sitokinlere benzer şekilde ÜK aktivasyonu ile ilişkili olduğunu ortaya koymaktadır. 

Supporting Institution

This study was supported by Selcuk University

Project Number

Project Number: 15102058

Thanks

Saygılarımla İyi çalışmalar dilerim

References

  • Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347(6):417-429. doi:10.1056/NEJMra020831
  • Funakoshi K, Sugimura K, Anezaki K, et al. Spectrum of cytokine gene expression in intestinal mucosal lesions of Crohn's disease and ulcerative colitis. Digestion. 1998;59(1):73-78. doi:10.1159/000007470
  • Mehlen P, Furne C. Netrin-1: When a neuronal guidance cue turns out to be a regulator of tumorigenesis. Cell Mol Life Sci. 2005;62(22):2599-2616. doi:10.1007/s00018-005-5191-3
  • Liu J, Du J, Cheng X, et al. Effect of netrin-1 anti-inflammatory factor on acute lung injury in sepsis rats. Med Sci Monit.  2019;25:7928-7935. doi:10.12659/MSM.917279
  • Zhaoheng L, Jing J, Weirong B, Jiao L, Xiyun S. Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti-inflammatory effect, molecular immunology. 2018;103:166-172. doi:10.1016/j.molimm.2018.08.021
  • Scharl M, Rogler G. Inflammatory bowel disease pathogenesis: What is new? Curr Opin Gastroenterol. 2012;28(4):301-309. doi:10.1097/MOG.0b013e328353e61e
  • Morote-Garcia JC, Rosenberger P, Nivillac NM, et al. Hypoxia-inducible factor-dependent repression of equilibrative nucleoside transporter 2 attenuates mucosal inflammation during intestinal hypoxia. Gastroenterology. 2009;136(2):607-618. doi:10.1053/j.gastro.2008.10.037
  • Aherne CM, Collins CB, Masterson JC, et al. Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis. Gut. 2012;61(5):695-705. doi:10.1136/gutjnl-2011-300012
  • Glover LE, Colgan SP. Hypoxia and metabolic factors that influence inflammatory bowel disease pathogenesis. Gastroenterology. 2011;140(6):1748-55. doi:10.1053/j.gastro.2011.01.056
  • Guimbaud R, Bertrand V, Chauvelot-Moachon L, et al. Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis. Am J Gastroenterol. 1998;93(12):2397-2404. doi:10.1111/j.1572-0241.1998.00694.x
  • Ranganathan P, Jayakumar C, Santhakumar M, et al. Netrin-1 regulates colon-kidney cross talk through suppression of IL-6 function in a mouse model of DSS-colitis. Am J Physiol Renal Physiol. 2013;304(9):F1187-1197. doi:10.1152/ajprenal.00702.2012
  • Tadagavadi RK, Wang W, Ramesh G. Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. J Immunol. 2010;185(6):3750-3758. doi:10.4049/jimmunol.1000435
  • Yang Y, Wang X, Moore DR, et al. TNF-α mediates macrophage-induced bystander effects through netrin-1. Cancer Res. 2012;72(20):5219-5229. doi:10.1158/0008-5472.CAN-12-1463
  • Collins CB, Aherne CM, Kominsky D, et al. Retinoic acid attenuates ileitis by restoring the balance between T-helper 17 and T regulatory cells. Gastroenterology. 2011;141(5):1821-1831. doi:10.1053/j.gastro.2011.05.049
  • Paradisi A, Maisse C, Bernet A, et al. NF-kappaB regulates netrin-1 expression and affects the conditional tumor suppressive activity of the netrin-1 receptors. Gastroenterology. 2008;135(4):1248-1257. doi:10.1053/j.gastro.2008.06.080
  • Rosenberger P, Schwab JM, Mirakaj V, et al. Corrigendum: Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia. Nat Immunol. 2015;16(5):544. doi:10.1038/ni0515-544a
  • Mirakaj V, Dalli J, Granja T, Rosenberger P, & Serhan C. N. Vagus nerve controls resolution and pro-resolving mediators of inflammation. Journal of Experimental Medicine. 2014;211(6):1037-1048. doi:10.1084/jem.20132103
  • Schlegel M, Köhler D, Körner A., Granja T, Straub A, Giera M, & Mirakaj V. The neuroimmune guidance cue netrin‐1 controls resolution programs and promotes liver regeneration. Hepatology. 2014;63(5):1689-1705. doi:10.1002/hep.28347
  • Mirakaj V, Thix CA, Laucher S, et al. Netrin-1 dampens pulmonary inflammation during acute lung injury. Am J Respir Crit Care Med. 2010;181(8):815-824. doi:10.1164/rccm.200905-0717OC
  • Ziegon L, Schlegel M. Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation. International Journal of Molecular Sciences, 2021;23(1):275. doi:10.3390/ijms23010275
  • Xia X, Yin K, Hu Z, et al. Netrin-1: An emerging player in inflammatory diseases. Cytokine & Growth Factor Reviews. 2022;64(4):46-56. doi:10.1016/j.cytogfr.2022.01.003
  • Goral V, Celenk T, Kaplan A, et al. Plasma cytokine levels in ulcerative colitis. Hepatogastroenterology. 2007;54(76):1130-1133.

The Significance of Netrin-1 Level in the Clinical Activity of Ulcerative Colitis, its Association between TNF-α and IL-6

Year 2022, Volume: 7 Issue: 2, 247 - 252, 01.06.2022
https://doi.org/10.26453/otjhs.931360

Abstract

Objective: We investigated the importance of netrin-1 levels in Ulcerative Colitis (UC) in clinical activity of the disease, and its association with other proinflammatory cytokines IL-6 and TNF-alpha.
Materials and Methods: This study was a case-control study and included 67 patients with UC (36 activated, 31 in remission) and 50 healthy controls. UC patients were divided into mild activation (n=21), moderate activation (n= 6) and severe activation (n= 9) groups according to the "Truelove Witts clinical activity index". 31 asymptomatic patients were considered to be in remission. Netrin-1, IL-6 and TNF-alpha measurements in plasma samples were made using ELISA assay kit.
Results: Between the patient group and the control group; there was a statistically significant difference between netrin-1, IL-6, TNF-alpha, (p<0.05 for all). The plasma netrin-1 mean of UC with severe activation groupwas statistically significantly higher than that of the mild activation, remission group and control group (p<0.05). Plasma netrin-1 mean of UC with modarate activation group was statistically significantly higher than that of the mild activation and remission group.
Conclusion: We found that plasma netrin-1 levels increase with disease severity in UC, similar to proinflammatory cytokines such as TNF-alpha and IL-6.

Project Number

Project Number: 15102058

References

  • Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347(6):417-429. doi:10.1056/NEJMra020831
  • Funakoshi K, Sugimura K, Anezaki K, et al. Spectrum of cytokine gene expression in intestinal mucosal lesions of Crohn's disease and ulcerative colitis. Digestion. 1998;59(1):73-78. doi:10.1159/000007470
  • Mehlen P, Furne C. Netrin-1: When a neuronal guidance cue turns out to be a regulator of tumorigenesis. Cell Mol Life Sci. 2005;62(22):2599-2616. doi:10.1007/s00018-005-5191-3
  • Liu J, Du J, Cheng X, et al. Effect of netrin-1 anti-inflammatory factor on acute lung injury in sepsis rats. Med Sci Monit.  2019;25:7928-7935. doi:10.12659/MSM.917279
  • Zhaoheng L, Jing J, Weirong B, Jiao L, Xiyun S. Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti-inflammatory effect, molecular immunology. 2018;103:166-172. doi:10.1016/j.molimm.2018.08.021
  • Scharl M, Rogler G. Inflammatory bowel disease pathogenesis: What is new? Curr Opin Gastroenterol. 2012;28(4):301-309. doi:10.1097/MOG.0b013e328353e61e
  • Morote-Garcia JC, Rosenberger P, Nivillac NM, et al. Hypoxia-inducible factor-dependent repression of equilibrative nucleoside transporter 2 attenuates mucosal inflammation during intestinal hypoxia. Gastroenterology. 2009;136(2):607-618. doi:10.1053/j.gastro.2008.10.037
  • Aherne CM, Collins CB, Masterson JC, et al. Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis. Gut. 2012;61(5):695-705. doi:10.1136/gutjnl-2011-300012
  • Glover LE, Colgan SP. Hypoxia and metabolic factors that influence inflammatory bowel disease pathogenesis. Gastroenterology. 2011;140(6):1748-55. doi:10.1053/j.gastro.2011.01.056
  • Guimbaud R, Bertrand V, Chauvelot-Moachon L, et al. Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis. Am J Gastroenterol. 1998;93(12):2397-2404. doi:10.1111/j.1572-0241.1998.00694.x
  • Ranganathan P, Jayakumar C, Santhakumar M, et al. Netrin-1 regulates colon-kidney cross talk through suppression of IL-6 function in a mouse model of DSS-colitis. Am J Physiol Renal Physiol. 2013;304(9):F1187-1197. doi:10.1152/ajprenal.00702.2012
  • Tadagavadi RK, Wang W, Ramesh G. Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. J Immunol. 2010;185(6):3750-3758. doi:10.4049/jimmunol.1000435
  • Yang Y, Wang X, Moore DR, et al. TNF-α mediates macrophage-induced bystander effects through netrin-1. Cancer Res. 2012;72(20):5219-5229. doi:10.1158/0008-5472.CAN-12-1463
  • Collins CB, Aherne CM, Kominsky D, et al. Retinoic acid attenuates ileitis by restoring the balance between T-helper 17 and T regulatory cells. Gastroenterology. 2011;141(5):1821-1831. doi:10.1053/j.gastro.2011.05.049
  • Paradisi A, Maisse C, Bernet A, et al. NF-kappaB regulates netrin-1 expression and affects the conditional tumor suppressive activity of the netrin-1 receptors. Gastroenterology. 2008;135(4):1248-1257. doi:10.1053/j.gastro.2008.06.080
  • Rosenberger P, Schwab JM, Mirakaj V, et al. Corrigendum: Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia. Nat Immunol. 2015;16(5):544. doi:10.1038/ni0515-544a
  • Mirakaj V, Dalli J, Granja T, Rosenberger P, & Serhan C. N. Vagus nerve controls resolution and pro-resolving mediators of inflammation. Journal of Experimental Medicine. 2014;211(6):1037-1048. doi:10.1084/jem.20132103
  • Schlegel M, Köhler D, Körner A., Granja T, Straub A, Giera M, & Mirakaj V. The neuroimmune guidance cue netrin‐1 controls resolution programs and promotes liver regeneration. Hepatology. 2014;63(5):1689-1705. doi:10.1002/hep.28347
  • Mirakaj V, Thix CA, Laucher S, et al. Netrin-1 dampens pulmonary inflammation during acute lung injury. Am J Respir Crit Care Med. 2010;181(8):815-824. doi:10.1164/rccm.200905-0717OC
  • Ziegon L, Schlegel M. Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation. International Journal of Molecular Sciences, 2021;23(1):275. doi:10.3390/ijms23010275
  • Xia X, Yin K, Hu Z, et al. Netrin-1: An emerging player in inflammatory diseases. Cytokine & Growth Factor Reviews. 2022;64(4):46-56. doi:10.1016/j.cytogfr.2022.01.003
  • Goral V, Celenk T, Kaplan A, et al. Plasma cytokine levels in ulcerative colitis. Hepatogastroenterology. 2007;54(76):1130-1133.
There are 22 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research article
Authors

Kemal Fidan 0000-0002-2186-4196

Mehmet Zahid Koçak 0000-0003-4419-409X

Abdullah Doğan 0000-0001-7721-3707

Huseyin Korkmaz 0000-0002-3518-1943

Project Number Project Number: 15102058
Publication Date June 1, 2022
Submission Date May 6, 2021
Acceptance Date April 5, 2022
Published in Issue Year 2022 Volume: 7 Issue: 2

Cite

AMA Fidan K, Koçak MZ, Doğan A, Korkmaz H. The Significance of Netrin-1 Level in the Clinical Activity of Ulcerative Colitis, its Association between TNF-α and IL-6. OTJHS. June 2022;7(2):247-252. doi:10.26453/otjhs.931360

Creative Commons License

Online Türk Sağlık Bilimleri Dergisi [Online Turkish Journal of Health Sciences (OTJHS)] is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access journal distributed under the terms of the Creative Commons Attribution License (CC BY-NC 4.0). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Click here to get help about article submission processes and "Copyright Transfer Form".