Toll-Like Receptors in Acute Kidney Injury

Vázquez‐Carballo, Cristina; Guerrero‐Hue, Melania; García‐Caballero, Cristina; Rayego‐Mateos, Sandra; Opazo-Ríos, Lucas; Morgado‐Pascual, José Luis; Herencia-Bellido, Carmen; Vallejo‐Mudarra, Mercedes; Cortegano, Isabel; Gaspar, Marı́a-Luisa; Andrés, Belen de; Egido, Jesús; Moreno, Juan Antonio

doi:10.3390/ijms22020816

Cited by 45 publications

(35 citation statements)

References 245 publications

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“…ROS is associated with ER stress [9,10] However, there are several unanswered questions such as the following: (a) the delayed treatment of CORM2 on AKI was not studied, (b) the detailed mechanisms involved in the inhibition of H 2 O 2 -mediated Fyn-ER stress signaling by CORM2 have not been explored, and (c) protocol of optimal delivery and dosing and the possible treatment of CO in human diseases have not been recognized yet. Further, tolllike receptors (TLRs), mainly TLR4, are an important player in inflammation and many other cellular processes in the progression of AKI [60]. Treatment of CORM2 attenuated the levels of TLR2 and TLR4/ROS and reduced inflammation in the lung [61].…”

Section: Discussionmentioning

confidence: 99%

CO-Releasing Molecule-2 Prevents Acute Kidney Injury through Suppression of ROS-Fyn-ER Stress Signaling in Mouse Model

Uddin

Jeong

Pak

et al. 2021

Oxidative Medicine and Cellular Longevity

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Acute kidney injury (AKI) most commonly appears in critically ill patients in hospitals. AKI is characterized as a quick deterioration of kidney function and has recently been identified to be tightly interlinked with chronic kidney diseases. The emerging major mediators of AKI include oxidative stress and endoplasmic reticulum (ER) stress. Carbon monoxide (CO) attenuates oxidative stress and ER stress in various cells, while Fyn, a member of the Src kinase family, is activated by oxidative stress and contributes to ER stress in skeletal muscle. Considering these, the objective of the current research was to determine (i) the involvement of Fyn in ER stress-mediated AKI and (ii) the effect of CO-releasing molecule-2 (CORM2) on reactive oxygen species- (ROS-) Fyn-ER stress-mediated AKI. Pretreatment with CORM2 (30 mg/kg) efficiently inhibited LPS (30 mg/kg)-induced oxidative stress, inflammation, and cellular apoptosis during AKI in C57BL/6J mice. Also, CORM2 efficiently suppressed the activation of Fyn and ER stress in AKI mice. Consistently, pretreatment with CORM2 inhibited oxidative stress, Fyn activation, ER stress, inflammation, and apoptosis in LPS- or H2O2-stimulated proximal epithelial tubular cells. Fyn inhibition using siRNA or an inhibitor (PP2) significantly attenuated ER stress responses in the cells. These data suggest that CORM2 may become a potential treatment option against ROS-Fyn-ER stress-mediated AKI.

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Section: Discussionmentioning

confidence: 99%

CO-Releasing Molecule-2 Prevents Acute Kidney Injury through Suppression of ROS-Fyn-ER Stress Signaling in Mouse Model

Uddin

Jeong

Pak

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…In the presence of similar target legends, TLRs are proteins with an evolved structure which play a vital function in the human innate immune system (Andrade‐Silva et al., 2018; Vázquez‐Carballo et al., 2021). The critical role of TLR in association with the innate immune system was first identified in the insect ( Drosophila ).…”

Section: Discussionmentioning

confidence: 99%

Crocetin attenuating Urinary tract Infection and adherence of uropathogenic E. coli in NRK‐52E cells via an inflammatory pathway

Yang¹,

Qiu²,

Zhou

et al. 2021

J Food Biochem

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Background and objective Urinary tract infections (UTI) are commonly treated with broad‐spectrum antibiotics, but treatment has limitation due to causes of nephrotoxicity in uroepithelial cells. Recently, the researcher focuses their research on alternative therapy for the treatment of UTI. This study evaluated the anti‐infectious effect of crocetin against adherence of pathogenic [2‐14C]‐acetate labeled Escherichia coli (MTCC‐729) to rat proximal renal tubular cells (NRK‐52E cells) and explores the possible mechanism of action. Materials and methods In vitro cytotoxicity and radio acetate labeled tests were performed on NRK‐52E cells. The rats were divided into five different groups as follows: normal control (NC), disease control (DC), and various doses of crocetin (1.25, 2.5, and 5 mg/kg) treated group rats. White blood cells in blood, urine, and bacterial colony counts were estimated at regular intervals. Pro‐inflammatory cytokines, such as interleukin‐6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1), interleukin‐10 (IL‐10), and interleukin‐8 (IL‐8), were also estimated. In the current study, we estimated the mRNA expression of toll‐like receptor‐4 (TLR‐4) and toll‐like receptor‐2 (TLR‐2) in the renal and bladder tissues. Results Crocetin significantly (p < .05) inhibited the adherence of E. Coli in NRK‐52E cells. Crocetin suppresses the lipid peroxidation (LPO) 42% in cells treated with H2O2 cells without crocetin. The white blood cells (WBC) count in blood and urine were augmented and crocetin treatment significantly (p < .05) reduced the WBC in urine and blood. The pro‐inflammatory cytokines, such as IL‐6, MCP‐1, IL‐10, and IL‐8, significantly (p < .05) increased in the DC group and crocetin significantly (p < .05) reduced the pro‐inflammatory cytokines. Dose‐dependent treatment of crocetin significantly reduced the mRNA expression of TLR2 and TLR4 in the renal and bladder tissues. Conclusion Crocetin considerably reduced the bacterial adherence to NRK‐52E cells, attenuated the H2O2 induced toxicity in NRK‐52E cells and also improved the renal tubular function, and reduced the inflammatory response via altering the inflammatory and antioxidant markers. Practical application As we all know that urinary tract infection is the most common disease worldwide. In this study, we scrutinized the protective effect of crocetin against urinary tract infection. Crocetin treatment considerably reduced the zone of inhibition and improved radioactivity. Crocetin significantly reduced the levels of cytokines and inflammatory mediators. Crocetin can be used as a protective drug in the treatment of urinary tract infections.

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“…LPS has been extensively investigated and acknowledged as one of the key triggers of lethal shock and is one of the primary drivers of cytokine storm [22]. LPS is thought to form a complex with LPS-binding protein (LBP) and CD14 and bind to TLR4 on the surface of macrophages, ultimately triggering an excessive immune response and causing multiorgan dysfunction due to a cytokine storm [23,24]. LPS is thus considered an important target for elimination as an upstream trigger of sepsis [25].…”

Section: Lps Recognition Systemsmentioning

confidence: 99%

Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

Moriyama

Nishida

2021

IJMS

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Sepsis is characterized by a dysregulated immune response to infections that causes life-threatening organ dysfunction and even death. When infections occur, bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns, bind to pattern recognition receptors, such as toll-like receptors, to initiate an inflammatory response for pathogen elimination. However, strong activation of the immune system leads to cellular dysfunction and ultimately organ failure. Damage-associated molecular patterns (DAMPs), which are released by injured host cells, are well-recognized triggers that result in the elevation of inflammatory cytokine levels. A cytokine storm is thus amplified and sustained in this vicious cycle. Interestingly, during sepsis, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. Thus, the concept of blood purification has evolved to include inflammatory cells and mediators. In this review, we summarize recent advances in knowledge regarding the role of lipopolysaccharides, cytokines, DAMPs, and neutrophils in the pathogenesis of sepsis. Additionally, we discuss the potential of blood purification, especially the adsorption technology, for removing immune cells and molecular mediators, thereby serving as a therapeutic strategy against sepsis. Finally, we describe the concept of our immune-modulating blood purification system.

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Toll-Like Receptors in Acute Kidney Injury

Cited by 45 publications

References 245 publications

CO-Releasing Molecule-2 Prevents Acute Kidney Injury through Suppression of ROS-Fyn-ER Stress Signaling in Mouse Model

CO-Releasing Molecule-2 Prevents Acute Kidney Injury through Suppression of ROS-Fyn-ER Stress Signaling in Mouse Model

Crocetin attenuating Urinary tract Infection and adherence of uropathogenic E. coli in NRK‐52E cells via an inflammatory pathway

Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

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