Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation

Rhee, Sang Hoon; Im, Eun‐Ok; Riegler, Martin; Kokkotou, Efi; O’Brien, Michael; Pothoulakis, Charalabos

doi:10.1073/pnas.0502174102

Cited by 198 publications

(205 citation statements)

References 33 publications

(42 reference statements)

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“…For instance, Tlr5 -/-mice spontaneously develop colitis that is crucially mediated by TLR4 signaling [54] to beneficial and detrimental effects of signaling induced by TLR5 and TLR4, respectively. Despite these overall beneficial effects of TLR5 signaling, administration of TLR5 agonists in DSS-injured colons aggravates colitis, indicating that TLR5 signaling can also be deleterious in the intestine [55,56]. Cell type specificity of TLR5 signaling likely plays a role in its differential outcomes for the host.…”

Section: Mechanisms Underlying the Dual Role Of Intestinal Nf-κb Actimentioning

confidence: 99%

NF-κB in the regulation of epithelial homeostasis and inflammation

2010

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The IκB kinase/NF-κB signaling pathway has been implicated in the pathogenesis of several inflammatory diseases. Increased activation of NF-κB is often detected in both immune and non-immune cells in tissues affected by chronic inflammation, where it is believed to exert detrimental functions by inducing the expression of proinflammatory mediators that orchestrate and sustain the inflammatory response and cause tissue damage. Thus, increased NF-κB activation is considered an important pathogenic factor in many acute and chronic inflammatory disorders, raising hopes that NF-κB inhibitors could be effective for the treatment of inflammatory diseases. However, ample evidence has accumulated that NF-κB inhibition can also be harmful for the organism, and in some cases trigger the development of inflammation and disease. These findings suggested that NF-κB signaling has important functions for the maintenance of physiological immune homeostasis and for the prevention of inflammatory diseases in many tissues. This beneficial function of NF-κB has been predominantly observed in epithelial cells, indicating that NF-κB signaling has a particularly important role for the maintenance of immune homeostasis in epithelial tissues. It seems therefore that NF-κB displays two faces in chronic inflammation: on the one hand increased and sustained NF-κB activation induces inflammation and tissue damage, but on the other hand inhibition of NF-κB signaling can also disturb immune homeostasis, triggering inflammation and disease. Here, we discuss the mechanisms that control these apparently opposing functions of NF-κB signaling, focusing particularly on the role of NF-κB in the regulation of immune homeostasis and inflammation in the intestine and the skin.

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Section: Mechanisms Underlying the Dual Role Of Intestinal Nf-κb Actimentioning

confidence: 99%

NF-κB in the regulation of epithelial homeostasis and inflammation

2010

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“…[65][66][67][68] The differential expression of PRRs at different sites may be related to the different microenvironments and the different roles of PRRs. 69,70 For example, TLR2 is revealed to be associated with epithelial growth, survival, and repair. 69,70 Of note, although epithelial cells express a wide range of PRRs, not all PRRs are engaged in C. albicans recognition, and only certain TLRs and CLRs on epithelial surfaces are reported to be engaged.…”

Section: Prrs Of Epithelial Cellsmentioning

confidence: 99%

“…69,70 For example, TLR2 is revealed to be associated with epithelial growth, survival, and repair. 69,70 Of note, although epithelial cells express a wide range of PRRs, not all PRRs are engaged in C. albicans recognition, and only certain TLRs and CLRs on epithelial surfaces are reported to be engaged. 71 After culturing epithelial cells with C. albicans yeasts, TLR2, TLR4, TLR6, and TLR9 genes' expression were activated.…”

Section: Prrs Of Epithelial Cellsmentioning

confidence: 99%

The role of pattern recognition receptors in the innate recognition ofCandida albicans

Zheng

Wang

et al. 2015

Virulence

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“…18 Flagellin also participates in the pathophysiology of colitis, and flagellin released from commensal bacteria in the gut might contribute to chronic bowel inflammation diseases. 19 The intravenous administration of flagellin in mice can elicit severe acute lung inflammation. 20 TLR5 signaling is a key molecular pathway that mediates lung inflammation during cystic fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Over-activation of TLR5 signaling by high-dose flagellin induces liver injury in mice

et al. 2014

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Flagellin is a potent activator of a broad range of cell types that are involved in innate and adaptive immunity. Therefore, it is a good adjuvant candidate for vaccines, and it might function as a biological protectant against both major acute radiation syndrome during cancer radiotherapy and a mitigator of radiation emergencies. However, accumulating evidence has implicated flagellin in the occurrence of some inflammatory diseases, such as acute lung inflammation, cardiovascular collapse and inflammatory bowel disease. The aim of this study was to elucidate whether only flagellin-TLR5 signaling activation plays a role in the pathophysiology of liver or whether some other flagellin activity also contributes to liver injury either via bacterial infections or during clinical applications. Recombinant flagellin proteins with or without TLR5-stimulating activity were used to evaluate the role of flagellin-TLR5 signaling in liver injury in wild-type and TLR5 KO mice. Gross lesions and large areas of hepatocellular necrosis were observed in liver tissue 12 h after the intraperitoneal administration of 100 or 200 mg flagellin (FliC) in a dose-and time-dependent manner in wild-type mice, but not in TLR5 KO mice. Deletion of the N-terminal or TLR5 binding domain of flagellin inhibited flagellin-induced inflammatory responses and the subsequent acute liver function abnormality and damage. These data confirmed that flagellin is an essential determinant of liver injury and demonstrated that the over-activation of TLR5 signaling by high-dose flagellin caused acute inflammatory responses, neutrophil accumulation and oxidative stress in the liver, which contributes to the progression and severity of flagellin-induced liver injury.

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Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation

Cited by 198 publications

References 33 publications

NF-κB in the regulation of epithelial homeostasis and inflammation

NF-κB in the regulation of epithelial homeostasis and inflammation

The role of pattern recognition receptors in the innate recognition ofCandida albicans

Over-activation of TLR5 signaling by high-dose flagellin induces liver injury in mice

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