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The relationship between B-cell lymphoma 2, interleukin-1β, interleukin-17, and interleukin-33 and the development of diabetic nephropathy

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Abstract

Background

Diabetic nephropathy (DN) is among the main complications of diabetes mellitus and has been a major factor of renal failure. This study was designed to address the association between beta-cell lymphoma-2 (Bcl-2), interleukin (IL)-1β, IL-17, and IL-33 and the development of DN.

Methods

In this study, 20 healthy volunteers and 100 patients were enrolled. According to their biochemical markers, the patients were categorized into five groups: diabetic, chronic renal disease, diabetic chronic renal disease, end-stage renal disease, and diabetic end-stage renal disease.

Results

Our results showed a noticeable elevation in IL-1β and IL-17 levels and a reduction in IL-33 and Bcl-2 levels in all investigated groups compared with those in the healthy group. Positive correlations were found between IL-1β and fasting blood sugar and between creatinine levels and IL-17, HbA1c%, and sodium levels. However, negative correlations were found between IL-33 and urea and sodium concentrations and between Bcl-2 and HbA1c% and creatinine levels.

Conclusions

The present data revealed a marked relationship between Bcl-2, IL-1β, IL-17, and IL-33 levels and the onset and progression of DN. Understanding the molecular pathways of these processes could be translated into the development of therapeutic strategies.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article.

References

  1. Shahbazian H, Rezaii I (2013) Diabetic kidney disease; review of the current knowledge. J Ren Inj Prev 2(2):73–80

    PubMed  PubMed Central  Google Scholar 

  2. Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T (2016) Diabetic kidney disease: worldwide difference of prevalence and risk factors. J Nephropharmacol 5(1):49–56

    PubMed  Google Scholar 

  3. Taha H, Mahmoud HH, Soliman AS, Taha MM, Mohammed RA (2019) The Association between Highly Sensitive C-Reactive Protein and Interleukin-18 with Nephropathy in a Sample of Type 1 Diabetic Egyptian Patients. Med J Cairo Univ 87(4):2393–2402

    Google Scholar 

  4. Qin J, Peng Z, Yuan Q, Li Q et al (2019) AKF-PD alleviates diabetic nephropathy via blocking the RAGE/AGEs/NOX and PKC/NOX Pathways. Sci Rep 9(1):4407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Donate-Correa J, Ferri CM, Sánchez-Quintana F et al (2021) Inflammatory Cytokines in Diabetic Kidney Disease: Pathophysiologic and Therapeutic Implications. Front Med (Lausanne) 7:628289

    Article  PubMed Central  Google Scholar 

  6. Donate-Correa J, Víctor G, Tagua VG et al (2019) Pentoxifylline for Renal Protection in Diabetic Kidney Disease. A Model of Old Drugs for New Horizons. J Clin Med 8:287

    Article  CAS  PubMed Central  Google Scholar 

  7. Zhang G, Lv Z, Zhao Y et al (2012) Inhibitory effect of tumor necrosis factor–α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes. Exp Ther Med 22:1242

    Article  CAS  Google Scholar 

  8. Abdel-Moneim A, Bakery HH, Allam G (2018) The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomed Pharmacother 101:287–292

    Article  CAS  PubMed  Google Scholar 

  9. Tang H, Liu N, Feng X et al (2021) Circulating levels of IL-33 are elevated by obesity and positively correlated with metabolic disorders in Chinese adults. J Transl Med 19(1):52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Opferman JT, Kothari A (2018) Anti-apoptotic BCL-2 family members in development. Cell Death Differ 25:37–45

    Article  CAS  PubMed  Google Scholar 

  11. Wu N, Shen H, Liu H et al (2016) Acute blood glucose fluctuation enhances rat aorta endothelial cell apoptosis, oxidative stress and pro-inflammatory cytokine expression in vivo. Cardiovasc Diabetol 15(1):109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Borkan SC (2016) The Role of BCL-2 Family Members in Acute Kidney Injury. Semin Nephrol 36(3):237–250

    Article  CAS  PubMed  Google Scholar 

  13. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  14. Bonnemaison ML, Marks ES, Boesen EI (2017) Interleukin–1beta as a driver of renal NGAL production. Cytokine 91:38–43

    Article  CAS  PubMed  Google Scholar 

  15. Abdel-Moneim A, Mahmoud B, Sultan EA, Mahmoud R (2000) Associationof erythrocytes indices and interleukin-1 beta with metabolic syndrome components. UTMJ 97(1):6–13

  16. Li J, Xu J, Qin X et al (2019) Acute pancreatic beta cell apoptosis by IL-1β is responsible for postburn hyperglycemia: Evidence from humans and mice. Biochim Biophys Acta Mol Basis Dis 1865(2):275–284

    Article  CAS  PubMed  Google Scholar 

  17. Lei Y, Devarapu SK, Motrapu M et al (2019) Interleukin-1β Inhibition for Chronic Kidney Disease in Obese Mice With Type 2 Diabetes. Front Immunol 10:1223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pirklbauer M, Sallaberger S, Staudinger P et al (2021) Empagliflozin Inhibits IL-1β-Mediated Inflammatory Response in Human Proximal Tubular Cells. Int J Mol Sci 22(10):5089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lei Y, Devarapu SK, Motrapu M, Cohen CD, Lindenmeyer MT, Moll S, Kumar SV, Anders HJ (2019) Interleukin-1β Inhibition for Chronic Kidney Disease in Obese Mice With Type 2 Diabetes. Front Immunol 10:1223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Palsamy P, Subramanian S (2011) Resveratrol protects diabetic kidney by attenuating hyperglycemia- mediated oxidative stress and renal inflammatory cytokines via Nrf2–Keap1 signaling. Biochim Biophys Acta 1812(7):719–731

    Article  CAS  PubMed  Google Scholar 

  21. Chen C, Shao Y, Wu X, Huang C, Lu W (2016) Elevated Interleukin-17 Levels in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. Biochem Physiol 5:206–217

    Article  CAS  Google Scholar 

  22. Cruz JA, Child EE, Amatya N et al (2017) Interleukin-17 signaling triggers degradation of the constitutive NF-κB inhibitor ABIN-1. Immunohorizons 1(7):133–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Liu T, Zhang L, Joo D, Sun SC (2017) NF-κB signaling in inflammation. Signal Transduct Target Ther 2:17023

    Article  PubMed  PubMed Central  Google Scholar 

  24. Iyoda M, Shibata T, Kawaguchi M et al (2010) IL-17A and IL-17F stimulate chemokines via MAPK pathways (ERK1/2 and p38 but not JNK) in mouse cultured mesangial cells: synergy with TNF-alpha and IL-1beta. Am J Physiol Renal Physiol 298:779–787

    Article  CAS  Google Scholar 

  25. Ma J, Li YJ, Chen X, Kwan T, Chadban SJ, Wu H (2019) Interleukin 17A promotes diabetic kidney injury. Sci Rep 9(1):2264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wen Y, Crowley SD (2018) Renal effects of cytokines in hypertension. Curr Opin Nephrol Hypertens 27(2):70–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Karbach S, Croxford AL, Oelze M et al (2014) Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease. Arterioscler Thromb Vasc Biol 34(12):2658–2668

    Article  CAS  PubMed  Google Scholar 

  28. Madhur MS, Lob HE, McCann LA et al (2010) Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension 55(2):500–507

    Article  CAS  PubMed  Google Scholar 

  29. Nguyen H, Chiasson VL, Chatterjee P, Kopriva SE, Young KJ, Mitchell BM (2013) Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension. Cardiovasc Res 97(4):696–704

    Article  CAS  PubMed  Google Scholar 

  30. Norlander AE, Saleh MA, Kamat NV et al (2016) Interleukin-17A regulates renal sodium transporters and renal injury in angiotensin II-induced hypertension. Hypertension 68(1):167–174

    Article  CAS  PubMed  Google Scholar 

  31. Peng X, Xiao Z, Zhang J, Li Y, Dong Y, Du J (2015) IL-17A produced by both 𝛄𝛅 T and Th17 cells promotes renal fibrosis via RANTES-mediated leukocyte infiltration after renal obstruction. J Pathol 235(1):79–89

    Article  CAS  PubMed  Google Scholar 

  32. Cortvrindt C, Speeckaert R, Moerman A, Delanghe JR, Speeckaert MM (2017) The role of interleukin-17A in the pathogenesis of kidney diseases. Pathology 49(3):247–258

    Article  CAS  PubMed  Google Scholar 

  33. Coto E, Gómez J, Suárez B et al (2015) Association between the IL17RA rs4819554 polymorphism and reduced renal filtration rate in the Spanish RENASTUR cohort. Hum Immunol 76(2–3):75–78

    Article  CAS  PubMed  Google Scholar 

  34. Linhartova PB, Kastovsky J, Lucanova S et al (2016) Interleukin-17A Gene Variability in Patients with Type 1 Diabetes Mellitus and Chronic Periodontitis: Its Correlation with IL-17 Levels and the Occurrence of Periodontopathic Bacteria. Mediators Inflamm. : ID 2979846

  35. Duan L, Huang Y, Su Q et al (2016) Potential of IL-33 for Preventing the Kidney Injury via Regulating the Lipid Metabolism in Gout Patients J Diabetes Res. : ID 1028401

  36. Ferhat M, Robin A, Giraud S et al (2018) Endogenous IL-33 Contributes to Kidney Ischemia Reperfusion Injury as an Alarmin. J Am Soc Nephrol 29:1272–1288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sabapathy V, Stremska ME, Mohammad S, Corey RL, Sharma PR, Sharma R (2019) Novel Immuno modulatory Cytokine Regulates Inflammation, Diabetes, and Obesity to Protect From Diabetic Nephropathy. Front Pharmacol 10:572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Stremska ME, Jose S, Sabapathy V et al (2017) IL233, a novel IL-2 and IL-33 hybrid cytokine, ameliorates renal injury. J Am Soc Nephrol 28:2681–2693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nile CJ, Barksby E, Jitprasertwong P, Preshaw PM, Taylor JJ (2010) Expression and regulation of interleukin-33 in human monocytes. Immunology 130(2):172–180

    Article  PubMed  PubMed Central  Google Scholar 

  40. Caner S, Usluoğulları CA, Balkan F, Büyükcam F, Kaya C, Saçıkara M, Koca C, Ersoy R, Çakır B (2014) Is IL-33 useful to detect early stage of renal failure? Ren Fail 36(1):78–80

    Article  CAS  PubMed  Google Scholar 

  41. Alabi TD, Brooks NL, Oguntibeju OO (2021) Leaf Extracts of Anchomanes difformis Ameliorated Kidney and Pancreatic Damage in Type 2 Diabetes. Plants (Basel) 10(2):300

    Article  CAS  Google Scholar 

  42. Kale J, Osterlund EJ, Andrews DW (2018) BCL-2 family proteins: changing partners in the dance towards death. Cell Death Differ 25(1):65–80

    Article  CAS  PubMed  Google Scholar 

  43. Borkan SC (2016) The Role of BCL-2 Family Members in Acute Kidney Injury. Semin Nephrol 36(3):237–250

    Article  CAS  PubMed  Google Scholar 

  44. Bălăşescu E, Cioplea M, Brînzea A, Nedelcu R, Zurac S, Ion DA (2016) Immunohistochemical Aspects of Cell Death in Diabetic Nephropathy. Rom J Intern Med 54(1):54–62

    PubMed  Google Scholar 

  45. Nour H, Zahran N, Abd Elhamid S et al (2016) The Role of BCL-2 and BAK Genes in Chronic Kidney Disease and Haemodialysis Patients. J glycom Metab 1(1):8–24

    Article  Google Scholar 

  46. Borkan SC (2016) The Role of BCL-2 Family Members in Acute Kidney Injury. Semin Nephrol 36(3):237–250

    Article  CAS  PubMed  Google Scholar 

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Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt

    Basant Mahmoud

  2. Molecular Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt

    Adel Abdel-Moneim

  3. Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Salah Salem St, 62511, Beni-Suef, Egypt

    Zinab Negeem & Ahmed Nabil

Authors
  1. Basant Mahmoud
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  2. Adel Abdel-Moneim
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  3. Zinab Negeem
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  4. Ahmed Nabil
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Contributions

All authors contributed to the study’s conception and design. Material preparation and data collection and analysis were performed by Basant Mahmoud, Adel Abdel-Moneim, and Ahmed Nabil. The first draft of the manuscript was written by Basant Mahmoud, Adel Abdel-Moneim, and Ahmed Nabil, and all authors commented on the previous versions of the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Ahmed Nabil.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

The Hospital’s Ethics Committee, Beni Suef, Egypt, approved all procedures (BSU/2017/9). Written informed consent was given by all participants in the study.

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Cite this article

Mahmoud, B., Abdel-Moneim, A., Negeem, Z. et al. The relationship between B-cell lymphoma 2, interleukin-1β, interleukin-17, and interleukin-33 and the development of diabetic nephropathy. Mol Biol Rep 49, 3803–3809 (2022). https://doi.org/10.1007/s11033-022-07221-7

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  • DOI: https://doi.org/10.1007/s11033-022-07221-7

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