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

Year 2022, , 247 - 252, 01.06.2022

Kemal Fidan , Mehmet Zahid Koçak , Abdullah Doğan , Huseyin Korkmaz

https://doi.org/10.26453/otjhs.931360

Cited By: 2

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. 

Keywords

Netrin-1, Ülseratif Kolit, TNF-alfa, IL-6

Supporting Institution

This study was supported by Selcuk University

Project Number

Project Number: 15102058

Thanks

Saygılarımla İyi çalışmalar dilerim

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

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.

Keywords

Netrin-1, Ulcerative Colitis, IL-6, TNF-alpha

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.