Toll-like receptors in acute liver injury and regeneration

Chen, Yongyan; Sun, Rui

doi:10.1016/j.intimp.2011.04.023

Cited by 60 publications

(63 citation statements)

References 133 publications

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“…For infections that involve Gram-negative bacteria, TLR4 is central to this integrated response through the sensing of LPS (2). However, TLR4 is expressed on many cell types, including leukocytes and parenchymal cells (5)(6)(7). In this study, we used cell type-specific KO mouse strains to characterize the function of TLR on macrophages and hepatocytes, cell types thought to be integral to the host response to sepsis in a clinically relevant model of peritonitis (9,28).…”

Section: Discussionmentioning

confidence: 99%

“…This spatial organization of TLRs may facilitate the recognition of the microbes based on their unique components that are most likely to be available for host detection within specific subcellular domains. However, specificity of TLR function is likely to be dictated by subcellular location, as well as by cell type, because TLRs are expressed on diverse cell types that have wide-ranging and complementary functions (4)(5)(6)(7). However, the integration of host responses to infection through the recognition of the same microbial molecule by different cells using the same receptor is poorly understood.…”

mentioning

confidence: 99%

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Lipopolysaccharide Clearance, Bacterial Clearance, and Systemic Inflammatory Responses Are Regulated by Cell Type–Specific Functions of TLR4 during Sepsis

Deng

Scott

Loughran

et al. 2013

The Journal of Immunology

171

137

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The morbidity associated with bacterial sepsis is the result of host immune responses to pathogens, which are dependent on pathogen recognition by pattern recognition receptors, such as TLR4. TLR4 is expressed on a range of cell types, yet the mechanisms by which cell-specific functions of TLR4 lead to an integrated sepsis response are poorly understood. To address this, we generated mice in which TLR4 was specifically deleted from myeloid cells (LysMTLR4KO) or hepatocytes (HCTLR4KO) and then determined survival, bacterial counts, host inflammatory responses, and organ injury in a model of cecal ligation and puncture (CLP), with or without antibiotics. LysM-TLR4 was required for phagocytosis and efficient bacterial clearance in the absence of antibiotics. Survival, the magnitude of the systemic and local inflammatory responses, and liver damage were associated with bacterial levels. HCTLR4 was required for efficient LPS clearance from the circulation, and deletion of HCTLR4 was associated with enhanced macrophage phagocytosis, lower bacterial levels, and improved survival in CLP without antibiotics. Antibiotic administration during CLP revealed an important role for hepatocyte LPS clearance in limiting sepsis-induced inflammation and organ injury. Our work defines cell type–selective roles for TLR4 in coordinating complex immune responses to bacterial sepsis and suggests that future strategies for modulating microbial molecule recognition should account for varying roles of pattern recognition receptors in multiple cell populations.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Lipopolysaccharide Clearance, Bacterial Clearance, and Systemic Inflammatory Responses Are Regulated by Cell Type–Specific Functions of TLR4 during Sepsis

Deng

Scott

Loughran

et al. 2013

The Journal of Immunology

171

137

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“…In this study, we PTPRO and TLR4 in LPS/D-GaIN induced acute necrotic hepatitis, namely, FH. FH is a lethal acute liver damage accompanied with complicated disorders of the HF development and progression, such as T cells, NKT cells, and macrophages as well as evidence supports that innate immune response to microbes plays an important role in the development of FH through TLRs [4,5,30,31]. Increased expression of TLR4 has been found in status of HCV, HBV infection and liver injury [9,10,32].…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 99%

“…Excessive activation and dysfunction of lymphocytes and fulminant hepatic failure. In addition, activation of toll-like receptors (TLRs) and its downstream signaling molecules are also involved in FH [4,5]. Macrophages are considered to play a critical role in the initiation, progression of acute liver injury as well as the resolution of liver damage in viral hepatitis [6].…”

mentioning

confidence: 99%

Aggravated Liver Injury but Attenuated Inflammation in PTPRO-Deficient Mice Following LPS/D-GaIN Induced Fulminant Hepatitis

Wang

Yan

et al. 2015

Cell Physiol Biochem

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Background/Aims: Critical roles of PTPRO and TLR4 have been implicated in hepatocellular carcinoma. However, little is known about their modifying effects on inflammation-related diseases in liver, particularly fulminant hepatitis (FH). We aim to investigate the potential role of PTPRO and its interaction with TLR4 in LPS/D-GaIN induced FH. Methods: A LPS/D-GaIN induced mouse FH model was used. RAW264.7 cells were transfected with PTPRO over-expressed lentiviral plasmids for further investigation. Results: The mortality of PTPRO KO mice is higher than WT mice after LPS/D-GaIN administration. Aggravated liver injury was demonstrated by increased level of serous ALT and AST and numerous hepatic cells death in PTPRO KO mice following LPS/D-GaIN administration. Interestingly, inflammation was attenuated in PTPRO-deficient mice following LPS/D-GaIN administration, which was suggested by decreased inflammatory cytokines (TNF-a, IFN-γ, IL-1ß, IL-6, IL-17A and IL-12) and cells infiltrating into spleen (CD3⁺IFN-γ⁺ cells, CD3⁺TNF-a⁺ cells, F4/80⁺/TLR4⁺ cells). A feedback regulation between PTPRO and TLR4 dependent on NF-γB signaling pathway was demonstrated in vivo and in vitro. Conclusion: PTPRO plays an important role in FH by interacting with TLR4. The crosstalk between PTPRO and TLR4 is a novel bridge linking innate immune and adaptive immune in acute liver injury.

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“…Because the liver is the lymphoid organ with an overwhelming innate immune system, it functions as a filter organ at the first line between the digestive tract and the rest of the body, receiving 80% of the blood supply through the portal vein. 38 Reticuloendothelial system (RES) depression plays an important role in the development of bacterial translocation. Also, the presence of RES depression has been reported in various liver injury models.…”

Section: Groups Necrosis Inflammationmentioning

confidence: 99%

Effects of Lycium barbarum on bacterial translocation in thioacetamide-induced liver injury in rats

et al. 2015

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Background and study aim: The aim of the present study was to investigate the effects of Lycium barbarum (LB) on bacterial translocation (BT) frequency in thioacetamide (TAA)-induced liver injury in rats. Materials and methods: Group 1 was the control. In group 2 (TAA), rats received TAA daily for 3 days. In group 3 (TAA+LB), Lycium barbarum was administered orally 25 mg/kg for 21 days prior to the first TAA injection. In group 4 (LB), rats received only Lycium barbarum. Results: In our study, Lycium barbarum treatment did not attenuate liver damage. Lycium barbarum treatment decreased ileal E. coli counts and intestinal damage but it did not alter BT frequency. Conclusions: In conclusion, the effects of Lycium barbarum on BT may be related to ongoing severe liver damage in this model.

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Toll-like receptors in acute liver injury and regeneration

Cited by 60 publications

References 133 publications

Lipopolysaccharide Clearance, Bacterial Clearance, and Systemic Inflammatory Responses Are Regulated by Cell Type–Specific Functions of TLR4 during Sepsis

Lipopolysaccharide Clearance, Bacterial Clearance, and Systemic Inflammatory Responses Are Regulated by Cell Type–Specific Functions of TLR4 during Sepsis

Aggravated Liver Injury but Attenuated Inflammation in PTPRO-Deficient Mice Following LPS/D-GaIN Induced Fulminant Hepatitis

Effects of Lycium barbarum on bacterial translocation in thioacetamide-induced liver injury in rats

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