Assessing miR-146a-5P with IL-6 and TLR-4 serum levels in diabetic mellitus patients with or without urinary tract infection


  • Rabiha Q. Thajel
  • Abdulameer M. Ghareeb
  • Qays A. M. Al-Khafaji



Diabetic mellitus, UPEC, IL-6, TLR-4, miR-146a-5p


Introduction and Aim: Diabetes is a chronic metabolic disease that affects glucose levels. This condition increases blood sugar and weakens immunity, damaging neutrophil function and urine antibacterial activity. IL-6 and TLR-4 are involved in inflammation and immune system control, while miR-146-5p may be a biomarker for diabetes. This study examines IL-6, TLR-4, and miR-146-5p in diabetics with and without UT infection.


Materials and Methods: In this study, blood samples were collected from 100 diabetic mellitus patients suffering from UTI in addition to 100 individuals apparently healthy as control. The serum levels of IL-6 and TLR-4 were detected using commercial BTlab brand ELISA kits. The plasma RNA expression level of the miR-146a-5p was determined by real time-PCR using a specific primer for miR-146a-5p with the U6 gene utilized as a reference gene.


Results: The results showed that diabetic patient’s group had a significantly higher response of IL-6 than controls (75.6 vs. 27.6). TLR-4 levels showed high levels in diabetic patients’ group (1.3) in comparison with the control group (0.441). Both IL-6 and TLR-4 levels showed a significant difference between the diabetic patients with UTI compared to control. The results revealed no-significant differences in the levels among both diabetic patients with UTI and patients without UTI. TLR-4 and IL-6 showed a significant inverse relationship while the relation between TLR-4 level and miR-146a-5p expression level showed a negative relationship.


Conclusion: The levels of IL-6, TLR-4, and miR-146-5p expression were found to be considerably greater in individuals with diabetes having UTIs compared to patients with diabetes alone. An inverse relationship existed between IL-6 and TLR-4 levels as well as between TLR-4 and miR-146a-5p. The expression levels of IL-6 and miR-146-5p were nearly equal.

Author Biographies

Rabiha Q. Thajel

Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Baghdad, Iraq

Abdulameer M. Ghareeb

Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Baghdad, Iraq

Qays A. M. Al-Khafaji

Consultant Immunologist, Kamal Al-Samarraee Hospital for Infertility and IVF, Baghdad, Iraq


Mikhael, E.M., Hassali, M.A., Hussain, S.A., Shawky, N. Self-management knowledge and practice of type 2 diabetes mellitus patients in Baghdad, Iraq: A qualitative study. Diabetes Metab Syndr Obes. 2018;12:1-17.

Vijayashankar, U., Rajalakshmi, R., Ramya, C.M., Kumar, B., Smitha, M.C. Effect of lifestyle intervention in Type II diabetes. Biomedicine. 2022 Jul 3;42(3):550-555.

Adu, M., Malibu, U., Malau-Aduli, A., Malau-Aduli, B. Enablers and barriers to effective diabetes self-management: A multi-national investigation. PLoS One. 2019;14(6): e0217771

Ahmed, A.G., Al Atrakji, M.Q., Alwattar, W.M. Antibacterial effect of ethanolic fraction of Medicago sativa extract on Escherichia coli in urinary tract infection. Biomedicine. 2023 May 4;43(02):655-659.

Ogaidi B., AL-Jobori, K., Ghareeb, A. Green synthesis of silver nanoparticles by Ricinus communis and investigate its antibacterial potential against methicillin-resistant Staphylococcus aureus (MRSA). Biochemical and Cellular Archives. 2021; 21(2):3731-3740.

Mohsin, M.R., AL-Rubaii, B.A. Bacterial growth and antibiotic sensitivity of Proteus mirabilis treated with anti-inflammatory and painkiller drugs. Biomedicine. 2023;43(2): 728-734.

Worku, G., Alamneh, Y., Abegaz, W. Prevalence of bacterial urinary tract infection and antimicrobial susceptibility patterns among diabetes mellitus patients attending Zewditu Memorial Hospital, Addis Ababa, Ethiopia.Infect Drug Resist. 2021;14: 1441-1454

Forson, A., Menkah, D., Quarchie, M., Dhikrullah, S., Olu-Taiwo, M., Codjoe F. Bacterial drug-resistance patterns and genetic diversity of bacteria-associated bacteriuria in diabetic patients in Ghana. IJID Regions. 2021; 1:142-149.

Berbudi, A., Rahmadika, N., Tjahjadi, A., Ruslami, R. Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev. 2021; 16(5):442-449.

Rasoulinejad, S., Akbari, A., Nasiri, K. Interaction of miR-146a-5p with oxidative stress and inflammation in complications of type 2 diabetes mellitus in male rats: Antioxidant and anti-inflammatory protection strategies in type 2 diabetic retinopathy. Iran J Basic Med Sci. 2021;24 (8):1078-1086.

Wang, X., Sundquist, J., Zöller, B. Role of miRNAs in the development and progression of type 2 diabetes mellitus. Diabetes/Metabolism Research and Reviews. 2018;34(7): e2994.

Villar-Fincheira, P., Sanhueza-Olivares, F., Norambuena-Soto, I., Cancino-Arenas, N., Hernandez-Vargas, F., Troncoso, R., et al., Role of Interleukin-6 in vascular health and disease. Front Mol Biosci. 2021;8: 641734.

Wang, S., Yang, Y., Suen, A., Zhu, J., Williams, B., Hu, J., et al., Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis. Iscience. 2021; 24(12). 103441.

Matsushita, K., Takeuchi, O., Standley, D. M., Kumagai, Y., Kawagoe, T., Miyake, T., et al., Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature.2013; 458(7242): 1185-1190.

Mohammed, A.M., Zayni, S.M., AL-Anee, M.M., Corial, F.I.,Al-Rubaee, A. Diagnostic and predictive values of IL-6 in a group of Iraqi patients with rheumatoid arthritis. Journal of the Faculty of Medicine Baghdad. 2023; 65(2):116-121.

Aboudounya, M., Heads R. COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 may bind and activate TLR4 to increase ACE2 expression, facilitating entry and causing hyper inflammation. Mediators Inflamm. 2021; 2021: 1-8.

Litak, J., Grochowski, C., Litak, J., Osuchowska, I., Gosik, K., Radzikowska, E., et al., TLR-4 Signaling vs. immune checkpoints, mirnas molecules, cancer stem cells, and wingless-signaling interplay in glioblastoma multiforme—Future Perspectives. International Journal of Molecular Sciences. 2020; 21(9): 3114.

Taganov, K., Boldin, M., Chang, K., Baltimore, D. NF-B-dependent induction of microRNA miR-146,an inhibitor targeted to signaling proteins of innate immune responses. PNAS. 2006;103(33):12481-12486.

Asmaa A. Muhaimeed, Abdulameer M. Ghareeb Prevalence of multi-antibiotic resistance marA and quorum sensing luxS genes and evaluation of biofilm formation in uropathogenic Escherichia coli. Iraqi Journal of Biotechnology. 2023; 22(1): 252-261.

Daryabor, G., Atashzar, M., Kabelitz, D., Meri S., Kalantar, K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Front Immunol. 2020;11: 1582.

Patil, S., Gondhali, G., Acharya, A. Role of initial and follow-up IL-6 (Interleukin-6) titre in COVID-19 pneumonia: A single center experience. Electronic Journal of General Medicine. 2022; 19(5): em390.

Oliveira, F., Bafica, A., Rosato, A.B., Favali, C.B., Costa, J.M., Cafe, V., et al., Lesion size correlates with leishmania antigen-stimulated TNF-levels in human cutaneous leishmaniasis. Am J Trop Med Hyg. 2011; 85(1):70-73.

Vázquez-Carballo, C., Guerrero-Hue, M., García-Caballero, C., Rayego-Mateos, S., Opazo-Ríos, L., Morgado-Pascual, J.L. et al., Toll-like receptors in acute kidney injury. International Journal of Molecular Sciences. 2021; 22(2): 816.

El-Mesallamy, H.O., Diab, M.R., Hamdy, N.M., Dardir, S.M. Cell-based regenerative strategies for treatment of diabetic skin wounds, a comparative study between human umbilical cord blood-mononuclear cells and calves' blood haemodialysate. PLoS ONE. 2014; 9(3): e89853.

Barutta, F., Corbetta, B., Bellini, S., Guarrera, S., Matullo, G., Scandella, M. et al., MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS. J Transl Med. 2021; 19(1):1-10.

El-Hini, S., El-Akad, A., Nagib, M. Study the level of micro RNA146 a in human serum in the diabetic patients. MJMR. 2020; 31(2): 184-188.

Abdul-Rahman, P. S., Lim, P. S., Hashim, O. H., Shuib, A. S. Activation of TLR4-dependent inflammatory pathway in type 2 diabetes mellitus: the effect of metformin. Journal of Inflammation Research. 2020; 13: 1239-1251.

Zhang, J., Wang, X., Zhang, Y., Yang, X., Liu, Y., Xu, Y. The role of TLR4 and IL-6 in patients with urinary tract infections. Journal of Clinical Laboratory Analysis. 2019; 33(5):e22843.

Kim, Y. H., Kwon, Y. S., Oh, D. H., Kim, K. S. Urinary toll-like receptor 4 and inflammatory cytokines in patients with acute pyelonephritis. Journal of Microbiology, Immunology, and Infection. 2016; 49(5):699-706.




How to Cite

Q. Thajel R, M. Ghareeb A, A. M. Al-Khafaji Q. Assessing miR-146a-5P with IL-6 and TLR-4 serum levels in diabetic mellitus patients with or without urinary tract infection. Biomedicine [Internet]. 2023 Nov. 9 [cited 2023 Dec. 2];43(5):1502-7. Available from:



Original Research Articles

Plum Analytics