Using of TLR2 and TLR4 as Biomarker of Sepsis Severity Detection

Authors

  • Farah Qahtan Younis Department of Biology, college of sciences, Mustansiriyah University
  • Ali Hussein Alwan Department of Biology, college of sciences, Mustansiriyah University
  • Neihaya Heikmat Zaki Department of Biology, college of sciences, Mustansiriyah University

DOI:

https://doi.org/10.23851/mjs.v29i2.370

Abstract

Our study has been aimed to find the relation between the expression of toll-like receptors 2, 4, level of TNF-α, IL-10 and soluble HLA-DR with the severity bacterial septic syndrome in Iraqi patients. The quantitative real-time PCR technique has been used for measure TLR2 and TLR4 gene expression in whole blood, and ELISA technique has been used for detection of cytokines TNF-α, IL-10 and soluble HLA-DR from 75 septic syndrome cases (nineteen of patients showed symptoms of systemic inflammatory response syndrome (SIRS); twenty-eight patients have sepsis, seventeen patients suffered from severe sepsis and eleven patients have septic shock) and 55 healthy controls (HC). TLR2 and TLR4 mRNA expression were higher significantly in the all patients (P< 0.05), TNF-α, IL-10 and sHLA-DR serum levels were significantly elevated in the serum of patients with septic syndrome compared with controls (P<0.05) except the level of HLA-DR in SIRS patients there were no differences with a healthy control group. Also, the results have been shown, there are significant differences in TLR2 and TLR4 between the stages of the septic syndrome and also a positive correlation between TLR 4 and concentration of sHLA-DR. According to the results of our study, we can conclude the possibility of using TLR 2 and TLR 4 expression to determine the severity of sepsis as a diagnostic biomarker.

References

Gao, J. W., Zhang, A. Q., Wang, X., Li, Z. Y., Yang, J. H., Zeng, L., and Jiang, J. X., Association between the TLR2 Arg753Gln polymorphism and the risk of sepsis: a meta-analysis. Critical Care. 19,1, 416, 2015. DOI: https://doi.org/10.1186/s13054-015-1130-3

Angus, D.C. and Van Der Poll, T., Severe sepsis and septic shock. NEJM. 369,9,, 840-851,2013. DOI: https://doi.org/10.1056/NEJMra1208623

Dwyer, J. One boy’s death moves state to action to prevent others. The New York Times, December 20, 2012.

ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Critical Care Medicine. 20, 864-874,1992. DOI: https://doi.org/10.1097/00003246-199206000-00025

Yang, Y. X., and Li, L.. Identification of potential biomarkers of sepsis using bioinformatics analysis. Exp Ther Med. 13,5, 1689-1696, 2017. DOI: https://doi.org/10.3892/etm.2017.4178

Dimcheva, Y., Kalinova, K., Dinkov, D., Georgiev, K., Brahomov, B., andKyazimova, E.,АppendicitisIn Childhood And Systemic Inflammatory Response Syndrome (SIRS). TJS. 13,4, 105,2015. DOI: https://doi.org/10.15547/tjs.2015.04.017

Vincent, J. L., Definition of sepsis and non-infectious SIRS. Sepsis and Noninfectious Inflammation. (2008)

Das, U., HLA-DR expression, cytokines and bioactive lipids in sepsis. AMS. 10,2, 325, 2014. DOI: https://doi.org/10.5114/aoms.2014.42586

Foley, N.M., Wang, J., Redmond, H.P. and Wang, J.H., Current knowledge and future directions of TLR and NOD signaling in sepsis. Military Medical Research. 2,1,1 (2015). DOI: https://doi.org/10.1186/s40779-014-0029-7

Kumar, H., Kawai, T. and Akira, S., Pathogen recognition by the innate immune system. International reviews of immunology. 30,1,16-34, 2011. DOI: https://doi.org/10.3109/08830185.2010.529976

Paredes-Juarez, G. A., de Haan, B. J., Faas, M. M., and de Vos, P., The role of pathogen-associated molecular patterns in inflammatory responses against alginate based microcapsules. JCR. 172,3, 983-992, 2013. DOI: https://doi.org/10.1016/j.jconrel.2013.09.009

Boomer, J.S., Green, J.M. and Hotchkiss, R.S., The changing immune system in sepsis: is individualized immuno-modulatory therapy the answer?. Virulence. 5,1, :45-56, 2014. DOI: https://doi.org/10.4161/viru.26516

Leentjens, J., Kox, M., van der Hoeven, J.G., Netea, M.G. and Pickkers, P., Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change?. AJRCCM. 187,12,1287-1293, 2013. DOI: https://doi.org/10.1164/rccm.201301-0036CP

Rebmann, V., Ugurel, S., Tilgen, W., Reinhold, U., and Grosse‐Wilde, H., Soluble HLA‐DR is a potent predictive indicator of disease progression in serum from early‐stage melanoma patients. IJC. 100,5, 580-585, 2002. DOI: https://doi.org/10.1002/ijc.10524

Adamashvili, I., Minagar, A., Gonzalez-Toledo, E., Featherston, L., and Kelley, R. E., Soluble HLA measurement in saliva and cerebrospinal fluid in Caucasian patients with multiple sclerosis: a preliminary study. Journal of neuroinflammation. 2,1, 13, 2005. DOI: https://doi.org/10.1186/1742-2094-2-13

Cho, S.Y. and Choi, J.H., Biomarkers of sepsis. Infection and chemotherapy. 46,1, 1-12, 2014. DOI: https://doi.org/10.3947/ic.2014.46.1.1

Salomao, R., Martins, P.S., Brunialti, M.K.C., da Luz Fernandes, M., Martos, L.S., Mendes, M.E., Gomes, N.E. and Rigato, O., TLR signaling pathway in patients with sepsis. Shock. 30, 7, 73-77, 2008. DOI: https://doi.org/10.1097/SHK.0b013e318181af2a

Akira, S., and Takeda, K., Toll-like receptor signalling. Nature Reviews Immunology. 4,7, 499-511, 2004. DOI: https://doi.org/10.1038/nri1391

Schaaf, B., Luitjens, K., Goldmann, T., van Bremen, T., Sayk, F., Dodt, C., Dalhoff, K. and Droemann, D., Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes. Diagnostic Pathology. 4,1, 12, 2009. DOI: https://doi.org/10.1186/1746-1596-4-12

Brunialti, M. K. C., Martins, P. S., de Carvalho, H. B., Machado, F. R., Barbosa, L. M., and Salomao, R., TLR2, TLR4, CD14, CD11B, and CD11C expressions on monocytes surface and cytokine production in patients with sepsis, severe sepsis, and septic shock. Shock 25,4, 351-357, 2006. DOI: https://doi.org/10.1097/01.shk.0000217815.57727.29

Tsujimoto, H., Ono, S., Efron, P. A., Scumpia, P. O., Moldawer, L. L., and Mochizuki, H., Role of Toll-like receptors in the development of sepsis. Shock. 29,3, 315-321, 2008. DOI: https://doi.org/10.1097/SHK.0b013e318157ee55

Droemann, D., Goldmann, T., Tiedje, T., Zabel, P., Dalhoff, K., Schaaf, B., Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respiratory Research. 6 1, 68,2005. DOI: https://doi.org/10.1186/1465-9921-6-68

Yusa, T., Tateda, K., Ohara, A., and Miyazaki, S., New possible biomarkers for diagnosis of infections and diagnostic distinction between bacterial and viral infections in children. JIC. 23, 2, 96-100, 2017. DOI: https://doi.org/10.1016/j.jiac.2016.11.002

Ghuge,G.D., Zine., R and MukundMogrekar., Evaluation of C-reactive protein and tumor necrosis factor- alpha as reliable laboratory markers for early diagnosis of sepsis. Int J Biol Med Res. 3,4, 2345-2347, 2012.

Kocabas, E., Sarikçioglu, A., Aksaray, N., andSeydaoglu, G., Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-[alpha] in the diagnosis of neonatal sepsis. The Turkish journal of pediatrics. 49, 1, 7, 2007.

Dinata, K., Runtunuwu, A. L., Mandei, J. M., and Lolombulan, J. H., Correlation between tumor necrosis factor-alpha and septic shock in children. Paediatrica Indonesiana. 53,1, 1-5,2013. DOI: https://doi.org/10.14238/pi53.1.2013.1-5

Nascimento, Daniele C., Paulo H. Melo, Annie R. Pineros, Raphael G. Ferreira, David F. Colón, Paula B. Donate, Fernanda V. Castanheira., "IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population." Nature Communications. 8, 2017. DOI: https://doi.org/10.1038/ncomms14919

Lekkou, A., Karakantza, M., Mouzaki, A., Kalfarentzos, F. and Gogos, C.A., Cytokine production and monocyte HLA-DR expression as predictors of outcome for patients with community-acquired severe infections. Clin Diagn Lab Immunol. 11,1, 161-167, 2004. DOI: https://doi.org/10.1128/CDLI.11.1.161-167.2004

Wu HP, Chen CK, Chung K, Tseng JC, Hua CC and Liu YC,. Serial cytokine levels in patients with severe sepsis. Inflamm Res. 57,385–93, 2009. DOI: https://doi.org/10.1007/s00011-009-0003-0

Del Vecchio, A., Ladisa, G., Laforgia, N., De Felice, C., Presta, G. and Latini, G., Genetic polymorphisms in neonatal sepsis. In Hematology Meeting Reports. 2, 10, 31-37, 2009.

Chaudhry, H., Zhou, J., Zhong, Y., Ali, M.M., McGuire, F., Nagarkatti, P.S. and Nagarkatti, M., Role of cytokines as a double-edged sword in sepsis. In Vivo.27, 6, 669-684, 2013.

Schulte, W., Bernhagen, J., and Bucala, R., Cytokines in sepsis: potent immunoregulators and potential therapeutic targets—an updated view. Mediators of inflammation. 2013,1-16, 2013. DOI: https://doi.org/10.1155/2013/165974

Perry, S. E., Mostafa, S. M., Wenstone, R., Shenkin, A., and McLaughlin, P. J, HLA-DR regulation and the influence of GM-CSF on transcription, surface expression and shedding. Int. J. Med. Sci.1,3, 126, 2004. DOI: https://doi.org/10.7150/ijms.1.126

Verbruggen, L. A., Versaen, H., Rebmann, V., Duquet, W., De Cock, S., Grosse-Wilde, H., and Demanet, C., Soluble HLA-DR levels in serum are associated with therapy and genetic factors in rheumatoid arthritis. Human immunology. 63, 9, 758-764, 2002. DOI: https://doi.org/10.1016/S0198-8859(02)00431-7

Verbruggen, L.A., Dumarey, N., Velde, H., Rebmann, V., Flament, J., Wayenberge, C., Grosse‐Wilde, H. and Demanet, C., Soluble HLA‐DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease‐associated epitopes. HLA. 56,5, 436-440, 2000. DOI: https://doi.org/10.1034/j.1399-0039.2000.560506.x

Matalliotakis, I. M., Athanassakis, I., Goumenou, A. G., Neonaki, M. A., Koumantakis, E. E., Vassiliadis, S., &Koumantakis, E. E., The possible anti-inflammatory role of circulating human leukocyte antigen levels in women with endometriosis after treatment with danazol and leuprorelin acetate depot. Mediators of inflammation. 10,2, 75-80, 2001. DOI: https://doi.org/10.1080/09629350120054545

Frei, R., Steinle, J., Birchler, T., Loeliger, S., Roduit, C., Steinhoff, D., Seibl, R., Büchner, K., Seger, R., Reith, W. and Lauener, R.P., MHC class II molecules enhance Toll-like receptor mediated innate immune responses. PloS one. 5,1, 8808, 2010. DOI: https://doi.org/10.1371/journal.pone.0008808

Hertz CJ, Kiertscher SM, Godowski PJ, Bouis DA, and NorgardMV,.. Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor. J Immunol. 166, 2444–2450,2001. DOI: https://doi.org/10.4049/jimmunol.166.4.2444

Lorne, E., Dupont, H., & Abraham, E ., Toll-like receptors 2 and 4: initiators of non-septic inflammation in critical care medicine?. ICM. 36,11, 1826-1835, 2010. DOI: https://doi.org/10.1007/s00134-010-1983-5

Downloads

Published

2018-11-17

How to Cite

[1]
F. Q. Younis, A. H. Alwan, and N. H. Zaki, “Using of TLR2 and TLR4 as Biomarker of Sepsis Severity Detection”, Al-Mustansiriyah Journal of Science, vol. 29, no. 2, pp. 83–92, Nov. 2018.

Issue

Section

Biological Science