Toll-Like Receptor 4 and CD14 Gene Polymorphisms in Tunisian Kidney Transplantation

Krichen, Henda; Gorgi, Yousr; Dhaouadi, Tarak; Mecheri, Y.; Sfar, Imen; Bardi, R.; Bacha, Mohamed Mongi; Abderrahim, E.; Jendoubi-Ayed, S.; Ayed, K.; Abdallah, T. Ben

doi:10.1016/j.transproceed.2013.09.003

Cited by 9 publications

(18 citation statements)

References 31 publications

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“…Opinions range from equal contributions to a more significant role of TLR4 on renal cells. 19,38 Neutrophils and PBMCs that have abundant TLR4 expression are readily attracted to inflammatory sites, 7 so the proportion of cells with low TLR4 and MyD88 expression may increase in monocytes that remain in circulation. 11 In clinical conditions, this phenomenon can be observed in kidney transplant recipients in whom the average TLR4 expression of PBMCs is low within the first 24 h after transplantation.…”

Section: Innate Immunity: From Brain Death To Reperfusion Injurymentioning

confidence: 99%

“…Analyses of CD14 allele and genotype distribution indicate a lower incidence of AR in homozygous wild-type CD14*C/C, but without statistical significance. 38 Most TLR4 polymorphisms (e.g., A299G/T399I) observed in renal transplant recipients have been connected with a decrease in TLR4 expression in monocytes and neutrophils. The A299G/T399I polymorphism presents a lower risk of atherosclerosis and AR.…”

Section: Acute Kidney Injurymentioning

confidence: 99%

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The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Zmonarski¹,

Banasik²,

Madziarska³

et al. 2019

Adv Clin Exp Med

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Krajewska M. The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells. AbstractThe innate immune system is activated before an adaptive immune response. An expression of a particular toll-like receptor (TLR) in a transplanted kidney depends on the localization of specific cells (e.g., endothelium, elements of the nephron structure), recent pathology and the time passed since transplantation. The TLR4 receptor is expressed on renal tubular epithelial (RTE) and endothelial cells, podocytes, blood and interstitial monocytes/macrophages, and dendritic cells. While circulating in blood, some monocytes are attracted and penetrate the transplanted organ, where they supplement the donor's resident macrophages. The intensity of migration depends on the local activation of inflammation in the graft and on the expression of specific receptors on kidney endothelial cells and monocytes/macrophages. The percentage of cells with shifted TLR4 expression usually increases in circulating monocytes. The TLR4 and the biochemical stimulation cascade derived from it in any type of cell, including monocytes, undergo multi-level regulation with feedback loops with other components of the primary system, and are also dependent on the action of immunosuppression. Toll-like receptor 4 senses stimuli that make monocytes contribute differently both to acute/chronic kidney injuries and to the development of tolerance. After kidney transplantation, TLR4 expression and related cytokine production capacity may vary depending on past diseases and oncoming problems. Since conventional immunosuppression does not prevent chronic allograft injury (CAI), peripheral blood monocytes and TLR4 constitute candidates for diagnostic and therapeutic targets. Considering the mutual communication among various elements of the primary immune system, future therapeutic intervention should be directed toward factors directly or indirectly regulating the expression or post-receptor signaling of the TLR4 receptor.

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Section: Innate Immunity: From Brain Death To Reperfusion Injurymentioning

confidence: 99%

Section: Acute Kidney Injurymentioning

confidence: 99%

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Zmonarski¹,

Banasik²,

Madziarska³

et al. 2019

Adv Clin Exp Med

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“…The TLR family is composed of 11 members, activating different intracellular events through signal transduction: production of cytokines, chemokines and cellular membrane proteins related to the inflammatory responses. TLR4 and its co-receptor CD14, are believed to initiate inflammation and tissue injury by responding to many various ligands (CD14 recognizes bacterial components) [17]. The complement system contributes an important element of the innate immune system, but also plays a role in adaptive immunity: complement component 3 (C3) plays a central role in the activation cascade.…”

Section: Cytokine Growth Factors Promoting T Cell Activationmentioning

confidence: 99%

“…The frequency of rejection episodes was similar between the two groups. The deletion is rare and several groups reporting lack of associations did not detect homozygous carriers [17,[33][34][35][36][37] (Table 3).…”

Section: Positive Associations In Kidney Transplant Recipientsmentioning

confidence: 99%

Genetic polymorphisms in the immune response: A focus on kidney transplantation

Stojanova

Pouché

Picard

2016

Clinical Biochemistry

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“…Patients with TLR4 mutations demonstrate reduced graft immune rejection. [15][16][17][18][19] Recently, some researchers have suggested that TLR2 plays an important role in xenograft rejection. HMGB1, an activated ligand of TLR2/4, is released in a rat-to-mouse heart xenograft model; specifically, blocking TLR2/4 signaling with an HMGB1-neutralizing antibody significantly prolonged xenograft survival and reduced immune rejection.…”

Section: Introductionmentioning

confidence: 99%

A potential role of TLR2 in xenograft rejection of porcine iliac endothelial cells: An in vitro study

Chen

Gao

Chen

et al. 2019

Xenotransplantation

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Background Porcine vascular endothelial cells are a major participant in xenograft rejection. The Toll‐like receptor 2 (TLR2) pathway plays an important role in both innate and adaptive immunity. The specific role of TLR2 in the response to a xenograft has not been reported. Whether the TLR2 pathway in pig vascular endothelial cells is involved in acute rejection needs to be investigated, and the mechanism is explored. Methods We used a modified antibody‐dependent complement‐mediated cytotoxicity (ADCC) assay to conduct in vitro experiments. In porcine iliac artery endothelial cells (PIECs), siRNA was used to knock down the expression of TLR2, CXCL8, and CCL2. The effect of human serum or inactivated human serum on the expression of TLR2 was analyzed by real‐time PCR and Western blotting, and transwell assays were used to assess the chemotactic efficiency of PIECs on human monocyte‐macrophages (THP‐1 cells) and human neutrophils. The downstream signaling pathways activated by human serum were detected by Western blotting, and the regulation of proinflammatory chemokines and cytokines by TLR2 signaling was assessed by real‐time PCR and ELISA. Results TLR2 was significantly upregulated in PIECs after exposure to human serum, and porcine proinflammatory chemokines, CXCL8 and CCL2, were induced, at least partially, in a TLR2‐dependent pattern; the upregulated chemokines participated in the chemotaxis of human neutrophils and THP‐1 cells across the species barrier. Conclusions (i) TLR2 is significantly upregulated in PIECs by human serum, (ii) the elevated TLR2 participates in the chemotaxis of inflammatory cells through the secretion of chemokine CCL2 and CXCL8, and (iii) blockade of TLR2 would be beneficial for xenograft survival.

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Toll-Like Receptor 4 and CD14 Gene Polymorphisms in Tunisian Kidney Transplantation

Cited by 9 publications

References 31 publications

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Genetic polymorphisms in the immune response: A focus on kidney transplantation

A potential role of TLR2 in xenograft rejection of porcine iliac endothelial cells: An in vitro study

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