Author(s): Amitha Ramesh, Sudhir Rama Varma, Srinivas Ramamurthy, Maher al Shayeb, Moyad Shahwan, Abed M. Atia Elkaseh, Al Moutassem Billah Khair, Adil Mageet, Madeeha Arif, Biju Thomas, Pavithra Jaganathan, Suchetha Shetty, Sharmila K.P

Email(s): s.varma@ajman.ac.ae

DOI: 10.5958/0974-360X.2021.00072.X   

Address: Amitha Ramesh1, Sudhir Rama Varma2,8, Srinivas Ramamurthy3, Maher al Shayeb2,8, Moyad Shahwan4,8, Abed M. Atia Elkaseh2,8, Al Moutassem Billah Khair5,8, Adil Mageet2,8, Madeeha Arif6, Biju Thomas1, Pavithra Jaganathan1, Suchetha Shetty7, Sharmila K.P7
1Department of Periodontics, A.B. Shetty Memorial Institute of Dental Sciences, Mangaluru, Karnataka, India.
2Department of Clinical sciences, College of Dentistry, Ajman University, Ajman, U.A.E.
3Department of Pharmaceutical Sciences, College of Pharmacy, University of Science and Technology of Fujairah, Fujairah, U.A.E.
4 Department of Clinical Sciences College of Pharmacy and Health Sciences, Ajman University, Ajman, U.A.E.
5 Department of Basic Sciences, College of Dentistry, Ajman University of, Ajman, U.A.E.
6 College of Dentistry, University of Science and technology of Fujairah, U.A.E.
7 Central Research Laboratory, Department of Biochemistry, K.S. Hegde Medical academy, Deralakattae, Mangaluru, Karnataka, India.

Published In:   Volume - 14,      Issue - 1,     Year - 2021


ABSTRACT:
Objective: The role of TLRs as principal signaling receptors in recognizing endotoxins on gram positive and negative bacteria is facilitated by TLRs and further enhances its role as a potential biomarker in assessing periodontal disease. The study aimed at evaluating the expression of sTLR2 and sTLR4 among healthy, periodontal and diabetic patients and further if there a comparable expression among the TLRs among genders. Material and Methods: Patients were selected according to pocket depth, Clinical attachment loss and radiographic bone loss. Unstimulated whole saliva was collected. sTLR2 and sTLR4 quantification was estimated by ELISA. Comparison of sTLRs between the study groups were performed using ANOVA followed by Tukey post Hoc test. Independent sample t test was used to compare between the genders. (p=0.05) Result: Expression of sTLR2 was higher among periodontitis patients compared to diabetic patients, this was also evident with relation to genders. sTLR4 showed significant expression among the three groups and also among the genders. Conclusion: The expression of sTLR2 was higher among periodontitis patients compared to diabetic patients. More studies need to be carried out to evaluate TLRs values among genders.


Cite this article:
Amitha Ramesh, Sudhir Rama Varma, Srinivas Ramamurthy, Maher al Shayeb, Moyad Shahwan, Abed M. Atia Elkaseh, Al Moutassem Billah Khair, Adil Mageet, Madeeha Arif, Biju Thomas, Pavithra Jaganathan, Suchetha Shetty, Sharmila K.P. Role of sToll-like receptors 2 and 4 in stage 2 periodontitis patients with and without type 2 diabetes: A Randomized clinical control trial. Research J. Pharm. and Tech. 2021; 14(1):397-404. doi: 10.5958/0974-360X.2021.00072.X

Cite(Electronic):
Amitha Ramesh, Sudhir Rama Varma, Srinivas Ramamurthy, Maher al Shayeb, Moyad Shahwan, Abed M. Atia Elkaseh, Al Moutassem Billah Khair, Adil Mageet, Madeeha Arif, Biju Thomas, Pavithra Jaganathan, Suchetha Shetty, Sharmila K.P. Role of sToll-like receptors 2 and 4 in stage 2 periodontitis patients with and without type 2 diabetes: A Randomized clinical control trial. Research J. Pharm. and Tech. 2021; 14(1):397-404. doi: 10.5958/0974-360X.2021.00072.X   Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-1-72


REFERENCES:
1.    Wong FS, Wen L. Toll-like receptors and diabetes. Annals of the New York Academy of Sciences. 2008; 1150(1): 123–132.
2.    Priscilla Naiff, Valéria Carneiro,  Maria do Carmo Guimarães . Importance of Mechanical Periodontal Therapy in Patients with Diabetes Type 2 and Periodontitis. International Journal of Dentistry. 2018; 2018: 692463.
3.    Shahwan MJ, et al. Prevalence of dyslipidemia and factors affecting lipid profile in patient with type 2 diabetes. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019 Jun 8; 13(4): 2387-2392.
4.    Jindal A, et al. Diabetes mellitus and periodontitis—a two-way relationship. PJSR. 2017; 10(2): 91–94.
5.    World Health Organization. Global Report on Diabetes. Geneva, Switzerland: World Health Organization; 2016.
6.    Sanz M, et al. Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. Diabetes Research and Clinical Practice. 2018; 137: 231–241.
7.    Sasanka S, et al. Global TLR2 and 4 Deficiency in mice impacts Bone resorption, Inflammatory Markers and Atherosclerosis to Polymicrobial Infection. Molecular Oral Microbiology. 2017 June; 32(3): 211–225.
8.    Lamont RJ, Hajishengallis G. Polymicrobial synergy and dysbiosis in inflammatory disease. Trends in Molecular Medicine. 2015; 21(3): 172-183.
9.    Gumus P. The Role of TLRs in the Pathogenesis of Periodontal Diseases. Journal of Dental Science and Therapy. 2016; 1(1): 3-6.
10.    Takeda K, Akira S. Toll-like receptors in immunity. International Immunology. 2005; 17(1): 1-14.
11.    Shahwan MJ, Khattab MH, Jairoun AA. Association of serum calcium level with waist circumference and other biochemical health-care predictors among patients with type 2 diabetes. Journal of pharmacy & bioallied sciences. 2019 Jul;11(3):292.
12.    Takeda K, Kaisho T, Akira S. Toll-like receptors. Annual Review of Immunology. 2003; 21: 335–376
13.    AlQallaf H, et al. Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic periodontitis. PLoS ONE. 2018; 13(12).
14.    Al Amiry A, Shahwan M. Vitamin D deficiency and associated factors among Ajman University students, United Arab Emirates. Obesity Medicine. 2020 Mar 1; 17: 100176.
15.    Beklen A, et al. Immunohistochemical localization of Toll-like receptors 1–10 in periodontitis. Oral Microbiology and Immunology. 2008; 23(5):425–31.
16.    Negative regulation of toll-like receptor-mediated immune responses. Nature Reviews Immunology. 2005; 5(6): 446-58.
17.    Oliveira-Nascimento L, Massari P, Wetzler LM. The role of TLR2 in infection and immunity. Frontiers in Immunology. 2012; 3: 79.
18.    Shahwan MJ, Gacem SA, Zaidi SK. Prevalence of Diabetic Nephropathy and associated risk factors among type 2 diabetes mellitus patients in Ramallah, Palestine. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019 Mar 1; 13(2): 149-6.
19.    Hajishengallis G, Darveau R, Curtis M. The keystone-pathogen hypothesis. Nature Reviews Microbiology. 2012; 10(10): 717-725.
20.    Hajishengallis G. Immunomicrobial pathogenesis of periodontitis-keystones, pathobionts, and host response. Trends in Immunology. 2014; 35(1): 1-11.
21.    Wang PL, et al. Toll-like receptor 4-mediated signal pathway induced by Porphyromonasgingivalis lipopolysaccharide in human gingival fibroblasts. Biochemical and Biophysical Research Communications. 2000; 273(3): 1161-1167.
22.    Akira S, Takeda K. Toll-like receptor signalling. Nature Reviews Immunology. 2004; 4(7): 499-511.
23.    Shahwan MJ, galil Hassan NA, Shaheen RA. Assessment of kidney function and associated risk factors among type 2 diabetic patients. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019 Jul 1; 13(4): 2661-5.
24.    Kusumoto Y, et al. Human gingival epithelial cells produce chemotactic factors interleukin-8 and monocyte chemoattractant protein-1 after stimulation with Porphyromonasgingivalis via toll-like receptor 2. Journal of Periodontology. 2004; 75(3): 370-379.
25.    Mori Y, et al. Immunohistochemical localization of Toll-like receptors 2 and 4 in gingival tissue from patients with periodontitis. Oral microbiology and immunology. 2003; 18(1): 54-58.  
26.    Curtiss LK, Tobias PS. Emerging role of Toll-like receptors in atherosclerosis. Journal of Lipid Research. 2009; 50: S340-S345.
27.    Dasu MR, et al. Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care. 2010 Apr; 33(4): 861-8.
28.    Tsan MF, Gao B. Endogenous ligands of Toll-like receptors. Journal of Leukocyte Biology. 2004; 76(3): 514-519.
29.    Reyna SM, et al. Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes. 2008; 57(10): 2596-2602.
30.    Creely SJ, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. American Journal of Physiology-Endocrinology and Metabolism. 2007; 292(3): E740-E747.
31.    Kim HS, et al. Toll-like receptor 2 senses beta- cell death and contributes to the initiation of autoimmune diabetes. Immunity. 2007; 27(2): 321-333.
32.    Song MJ, et al. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. Biochemical and Biophysical Research Communications. 2006; 346(3): 739-745.
33.    Yazdanpanah S, et al. Evaluation of glycated albumin (GA) and GA/HbA1c ratio for diagnosis of diabetes and glycemic control: A comprehensive review. Crit Rev Clin Lab Sci. 2017 Jun; 54(4): 219-232.
34.    Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018 Jun; 89: S159-S172.
35.    Prakasam S, Srinivasan M. Evaluation of salivary biomarker profiles following non-surgical management of chronic periodontitis. Oral Dis. 2014; 20(2): 171-7.
36.    Tu S, et al. Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases. International journal of molecular sciences. 2016; 17(8): 1288.
37.    Abdul-Cader MS, Amarasinghe A, Abdul-Careem MF. Activation of toll-like receptor signaling pathways leading to nitric oxide-mediated antiviral responses. Arch Virol. 2016;161(8):2075-86.
38.    LIN M. et al. Different engagement of TLR2 and TLR4 in Porphyromonas gingivalis vs.ligature-induced periodontal bone loss. Brazilian Oral Research. 2017 Aug 21; 31.
39.    Oliveira NF, et al. TLR2 and TLR4 gene promoter methylation status during chronic periodontitis. Journal of clinic Periodontology. 2011; 38(11): 975-83.
40.    Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nature Reviews Immunology. 2015; 15(1): 30-44.
41.    Rojo-Botello NR, Garcia-Hernandez AL, Moreno-Fierros L. Expression of toll-like receptors 2, 4 and 9 is increased in gingival tissue from patients with type 2 diabetes and chronic periodontitis. Journal of Periodontal Research. 2012; 47(1): 62–73.
42.    Ten Oever J, et al. The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases. BMC Immunol. 2014; 15(1): 55.
43.    AlQallaf H, et al. Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic Periodontitis. PLOS ONE. 2018; 13(12).
44.    Lappin DF, Sherrabeh S, Erridge C. Stimulants of Toll-like receptors 2 and 4 are elevated in saliva of periodontitis patients compared with healthy subjects. Journal of Clinic Periodontology. 2011; 38(4): 318–25.
45.    Isaza-Guzman DM, et al. Estimation of sCD14 levels in saliva obtained from patients with various periodontal conditions. Oral Dis. 2008; 14(5): 450–6.
46.    Nicu EA, et al. Soluble CD14 in periodontitis. Innate Immun. 2009; 15(2): 121–8.
47.    Rojo-Botello NR, Garcia-Hernandez AL, Moreno-Fierros L. Expression of toll-like receptors 2, 4 and 9 is increased in gingival tissue from patients with type 2 diabetes and chronic periodontitis. Journal of periodontal research. 2012; 47(1): 62–73.
48.    Shlossman M, et al. Type 2 diabetes mellitus and periodontal disease. The Journal of the American Dental Association. 1990; 121(4): 532–536.
49.    Taylor GW, et al. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. Journal of periodontology. 1998; 69(1): 76–83.
50.    Zaharieva E, et al. Reduced soluble Toll-like receptors 2 in type 2 diabetes. Arch Physiol Biochem. 2018 Oct; 124(4): 326-329.
51.    Promsudthi A, Poomsawat S, Limsricharoen W. The role of Toll-like receptor 2 and 4 in gingival tissues of chronic periodontitis subjects with type 2 diabetes. Journal of periodontal research. 2014 Jun; 49(3): 346-54.
52.    Rojo-Botello NR, García-Hernández AL, Moreno-Fierros L. Expression of toll-like receptors 2, 4 and 9 is increased in gingival tissue from patients with type 2 diabetes and chronic periodontitis. Journal of periodontal research. 2012 Feb; 47(1): 62-73.
53.    Shahwan MJ, et al. Association between abnormal serum hepatic enzymes, lipid levels and glycemic control in patients with type 2 diabetes mellitus. Obesity Medicine. 2019 Dec 1; 16: 100137.
54.    Devaraj S, et al. Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes. Diabetologia. 2009; 52(8): 1665–1668.
55.    Osterloh A, Breloer M. Heat shock proteins: linking danger and pathogen recognition. Medical microbiology and immunology. 2008; 197(1): 1–8.
56.    Martínez-García MA, et al. TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones. Biomolecules. 2020; 10(1): 111.
57.    Martinez-Garcia MA, et al. Postprandial inflammatory responses after oral glucose, lipid and protein challenges: Influence of obesity, sex and polycystic ovary syndrome. Clinical Nutrition. 2020; 39(3): 876-885.
58.    Fan H, Cook JA. Molecular mechanisms of endotoxin tolerance. Journal of endotoxin research. 2004; 10(2): 71–84.
59.    Zhang H, et al. Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach. Proteomics. 2010; 10(15): 2780–2789.
60.    Madhumitha H, et al. Impaired toll-like receptor signalling in peripheral B cells from newly diagnosed type-2 diabetic subjects. Cytokine. 2015; 76(2): 253–259.
61.    Scholtes VP, et al. Toll-like receptor 2 and 4 stimulation elicits an enhanced inflammatory response in human obese patients with atherosclerosis. Clinical Science. 2011; 121(5): 205–214.
62.    Markle JG, Fish EN. Sex matters in immunity. Trends in immunology. 2014; 35(3): 97–104.
63.    Leimgruber C, et al. Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated phenotype. Journal of cellular physiology. 2013; 228(7): 1551–1560.
64.    Jitprasertwong P, et al. Female sex hormones modulate Porphyromonas gingivalis lipopolysaccharide-induced Toll-like receptor signaling in primary human monocytes. Journal of periodontal research. 2016; 51(3): 395–406.
65.    Dennison U, et al. Menstrual cycle influences Toll-like receptor responses. Neuroimmunomodulation. 2012; 19(3): 171-9.
66.    Hirata T, et al. Expression of toll-like receptors 2, 3, 4, and 9 genes in the human endometrium during the menstrual cycle. Journal of reproductive immunology. 2007 Jun; 74(1-2): 53-60.
67.    Leifer CA, Medvedev AE. Molecular mechanisms of regulation of Toll-like receptor signaling. Journal of leukocyte biology. 2016; 100(5): 927–41.
68.    Tehrani M, et al. Decreased levels of soluble Toll-like Receptor 2 in patients with asthma. Reports of biochemistry & molecular biology. 2012; 1(1): 30–6.
69.    Candia E, et al. Increased production of soluble TLR2 by lamina propria mononuclear cells from ulcerative colitis patients. Immunobiology. 2012; 217(6): 634–42.

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