Toll-like receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with type 2 diabetes and diabetic foot

Wifi, Mohamed-Naguib; Assem, Maha; Elsherif, Rasha; El-Azab, Hameda Abdel-Fattah; Saif, Aasem

doi:10.1097/md.0000000000006760

Cited by 20 publications

(19 citation statements)

References 33 publications

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“…TLR9 gene polymorphism rs352139 is associated with increased risk of Tuberculosis (TB) in Mexican population but it is associated with decreased risk of TB in Indonesian population [418]. A link between TLR9-1237 T/C gene polymorphism and molecular risk for diabetes foot (DF) disease in patients with T2DM is also observed [419].…”

Section: Tlr Polymorphism In Humans and Their Disease Associationmentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

526

346

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The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.

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Section: Tlr Polymorphism In Humans and Their Disease Associationmentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

526

346

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“…We also show that the TLR3 protein level is elevated in the wound-edge epidermis of human diabetic foot ulcers, venous ulcers, and pressure ulcers, contributing to the increased neutrophil and macrophage infiltration in these chronic wounds [ 144 ]. A single-nucleotide polymorphism (SNP) study revealed that TLR4 and TLR9 SNPs and their haplotypes may increase the risk of impaired wound healing in type 2 diabetic patients [ 166 , 167 ]. In line with this, in a streptozotocin (STZ)-induced diabetes mouse model, knockout of TLR2 improved wound healing and reduced oxidative stress, MyD88 signaling, NF-κB activation, and cytokine secretion, suggesting that sustained TLR2 expression and activation may be detrimental to diabetic wounds [ 168 ].…”

Section: Impaired Immune Functions Of Keratinocytes In Chronic Nonmentioning

confidence: 99%

The Immune Functions of Keratinocytes in Skin Wound Healing

Piipponen

Landén

2020

IJMS

276

139

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As the most dominant cell type in the skin, keratinocytes play critical roles in wound repair not only as structural cells but also exerting important immune functions. This review focuses on the communications between keratinocytes and immune cells in wound healing, which are mediated by various cytokines, chemokines, and extracellular vesicles. Keratinocytes can also directly interact with T cells via antigen presentation. Moreover, keratinocytes produce antimicrobial peptides that can directly kill the invading pathogens and contribute to wound repair in many aspects. We also reviewed the epigenetic mechanisms known to regulate keratinocyte immune functions, including histone modifications, non-protein-coding RNAs (e.g., microRNAs, and long noncoding RNAs), and chromatin dynamics. Lastly, we summarized the current evidence on the dysregulated immune functions of keratinocytes in chronic nonhealing wounds. Based on their crucial immune functions in skin wound healing, we propose that keratinocytes significantly contribute to the pathogenesis of chronic wound inflammation. We hope this review will trigger an interest in investigating the immune roles of keratinocytes in chronic wound pathology, which may open up new avenues for developing innovative wound treatments.

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“…Literature data from recent years indicate that an important role in diabetic nephropathy etiopathogenesis may be played by signal transduction pathways that are dependent on TLR2, TLR9, and TLR4 receptors. However, it is not clear which receptor is more pathogenic [154,[158][159][160]. Studies of many research teams indicate increased expression of TLR2 and the presence of endogenous ligands HMGB1 [161,162] and HSP70 [107,122,163], detected on the basis of research conducted on diabetic-induced rats.…”

Section: Diabetic Nephropathy (Dn)mentioning

confidence: 99%

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

Mertowski

Lipa

Morawska

et al. 2020

IJMS

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One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. The growing number of studies on the role of TLR (toll-like receptor) receptors in the pathogenesis of kidney disease forces contemporary researchers to reflect on these molecules, which may soon join the group of renal biomarkers and become a helpful tool in the diagnosis of glomerulopathy. In this article, we conducted a thorough review of the literature on the role of TLRs in the pathogenesis of glomerulopathy. The role of TLR receptors as potential marker molecules for the development of neoplastic diseases is emphasized more and more often, as prognostic factors in diseases on several epidemiological backgrounds.

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Toll-like receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with type 2 diabetes and diabetic foot

Cited by 20 publications

References 33 publications

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

The Immune Functions of Keratinocytes in Skin Wound Healing

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

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