Toll-Like Receptors and their Role in Renal Pathologies

Eleftheriadis, Theodoros; Pissas, Georgios; Liakopoulos, Vassilios; Stefanidis, Ioannis; Lawson, Brian R.

doi:10.2174/187152812803589994

Cited by 48 publications

(40 citation statements)

References 89 publications

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“…TLR4 is a type of immune receptor expressed on cell surfaces that can be activated by IRI, triggering the TLR4 signaling pathway [43]. The TLR4-activating signal is transmitted through the adaptor protein MyD88, which is associated with activated TLRs and enhances further signaling cascades that activate the inflammation-related protein NF-κB [44, 45]. In IRI, NF-κB is activated by phosphorylation of IκB, leading in turn to activation of the IKK complex, which regulates proinflammatory responses [22, 23, 46].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Wang

et al. 2018

Cell Physiol Biochem

100

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Background: Ischemia-reperfusion injury (IRI) is one of the major causes of postoperative renal allograft dysfunction, which is mainly the result of proinflammatory reactions including inflammatory responses, oxidative stress, and metabolic disorders. Resveratrol (RSV) plays an important role in protecting various organs in IRI because it reduces oxidative stress, lessens the inflammatory response, and exerts anti-apoptotic effects. The aim of this study was to demonstrate the renoprotective effect of RSV in inhibiting inflammatory responses, reducing oxidative stress, and decreasing cell apoptosis in vivo and in vitro. Methods: RSV was administered before renal ischemia and H₂O₂ induction. Serum and kidneys were harvested 24 h after reperfusion and NRK-52E cells were collected 4 h after H₂O₂ stimulation. Serum creatinine and blood urea nitrogen were used to assess renal function. Hematoxylin and eosin staining was performed to assess histological injury. Quantitative real-time PCR and enzyme-linked immunosorbent assay were used to assess proinflammatory cytokine expression. Oxidative stress–related proteins, such as Nrf2 and TLR4, were evaluated by western blot. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling assay was used to detect apoptotic cells in tissues, and western blot was used to evaluate the expression of caspase-3, -8, and -9 in this study. Results: RSV inhibited inflammatory responses and improved renal function after renal IRI. Additionally, RSV decreased oxidative stress and reduced cell apoptosis by upregulating Nrf2 expression, downregulating the TLR4/NF-κB signaling pathway, and by decreasing caspase-3 activity and caspase cascades. Conclusion: Our study demonstrated the mechanisms underlying RSV renoprotection. We found that RSV exerts its greatest effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the Nrf2/TLR4/NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Wang

et al. 2018

Cell Physiol Biochem

100

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“…Cytokines play critical roles in orchestrating the rapid effective response of leukocytes and parenchymal cells to the detection of microorganisms or significant noninfective damage to parenchymal cells. These cells are hardwired with receptors that recognize and respond to common pathogen proteins through Toll-like receptors (TLRs) and danger-associated molecular pattern receptors (1). Although leukocytes are the major source of innate cytokine responses, parenchymal cells are increasingly recognized as also producing innate inflammatory cytokines and interacting with leukocytes to optimize cytokine responses in generating host defense.…”

Section: Innate Immunitymentioning

confidence: 99%

Cytokines

Holdsworth

Gan

2015

Clinical Journal of the American Society of Nephrology

118

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Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.

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“…Toll-like receptors (TLRs) were established as moderators of renal inflammation (Valles et al 2012). They are expressed in various cell types, including renal epithelial cells (Eleftheriadis and Lawson 2009;Eleftheriadis et al 2012). TLR4 is a further regulator of NF-κB .…”

Section: Effect Of Hsp70 On Pro-inflammatory Activation Of Epithelialmentioning

confidence: 99%

Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

Mazzei

Docherty

Manucha

2015

Cell Stress and Chaperones

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Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D, and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation, and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may affect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.

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Toll-Like Receptors and their Role in Renal Pathologies

Cited by 48 publications

References 89 publications

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Cytokines

Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

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