Possible involvement of reactive oxygen species in D‐galactosamine–induced sensitization against tumor necrosis factor‐α–induced hepatocyte apoptosis

Osawa, Yosuke; Nagaki, Masahito; Banno, Yoshiko; Yamada, Yasuhiro; Imose, Motoaki; Nozawa, Yoshinori; Moriwaki, Hisataka; Nakashima, Shigeru

doi:10.1002/jcp.1088

Cited by 43 publications

(32 citation statements)

References 45 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3A-B, upper panels), suggesting that TNF-␣ activated NF-B in hepatocytes in vivo as previously reported. 22 There was no nuclear translocation of p65 and no GFP expression in either the right or left lobe of PBDL livers (Fig. 3A-B, lower panels).…”

Section: Apoptotic Effect Of Tnf-␣ In Nf-b-suppressed Liver In Bdl MImentioning

confidence: 89%

Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver†

et al. 2005

Self Cite

View full text Add to dashboard Cite

Section: Apoptotic Effect Of Tnf-␣ In Nf-b-suppressed Liver In Bdl MImentioning

confidence: 89%

Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver†

et al. 2005

Self Cite

View full text Add to dashboard Cite

“…It has been reported that the PI 3-kinase/Akt pathway mediates hepatocyte survival (52). Selenoprotein P, which functions as a phospholipid hydroperoxide glutathione peroxidase, could protect TNF-␣-induced hepatocyte apoptosis (36).…”

Section: Discussionmentioning

confidence: 99%

Role of Toll-Like Receptors in Changes in Gene Expression and NF-κB Activation in Mouse Hepatocytes Stimulated with Lipopolysaccharide

et al. 2002

View full text Add to dashboard Cite

The liver is an important site of host-microbe interaction. Although hepatocytes have been reported to be responsive to lipopolysaccharide (LPS), the global gene expression changes by LPS and mechanism(s) by which LPS stimulates cultured hepatocytes remain uncertain. Cultures of primary mouse hepatocytes were incubated with LPS to assess its effects on the global gene expression, hepatic transcription factors, and mitogen-activated protein (MAP) kinase activation. DNA microarray analysis indicated that LPS modulates the selective expression of more than 80 genes and expressed sequence tags. We have shown previously that hepatocytes express CD14, which is required both for uptake and responsiveness to LPS. In other cells, responsiveness to microbial products requires expression of Toll-like receptors (TLR) and their associated accessory molecules. Hepatocytes expressed TLR1 through TLR9 as well as MyD88 and MD-2 transcripts, as shown by reverse transcriptase PCR analysis, indicating that hepatocytes express all known microbe recognition molecules. The MAP kinase extracellular signal-regulated kinase 1/2 was phosphorylated in response to LPS in mouse hepatocytes, and the levels of phosphorylation were lower in hepatocytes from TLR4-null mice. NF-B activation was reduced in TLR4-mutant or -null hepatocytes compared to control hepatocytes, and this defect was partially restored by adenoviral transduction of mouse TLR4. Thus, hepatocytes respond to nanogram concentrations of LPS through a TLR4 response pathway.Lipopolysaccharide (LPS), a glycolipid constituent of the outer membrane of gram-negative bacteria, initiates signaling cascades in cells such as macrophages and endothelial cells, leading to the release of cytokines and other inflammatory mediators during sepsis. Excessive production of these mediators can cause septic shock and multiple organ failure (55).A decade ago, CD14, a 55-kDa glycoprotein and monocyte differentiation antigen, was identified as an important LPS recognition molecule (60). CD14 alone, however, is unable to transduce the intracellular LPS signal, since CD14 is only tethered to the cytoplasmic membrane by a glycosyl phosphatidylinositol anchor and lacks a membrane-spanning domain (17). Members of a family of proteins, the mammalian homologues of the Drosophila Toll protein, were found to act as transmembrane coreceptors to CD14 in the cellular response to LPS (34). These Toll-like receptors (TLR) contain ectodomains with leucine-rich repeats, and their intracellular motifs are highly homologous to intracellular signaling domains of interleukin-1 receptor type I (IL-1RI) and IL-1RI accessory protein (reviewed in reference 5). Following dimerization of the TLR, these domains attract the adapter protein MyD88, which in turn recruits the IL-1R-associated kinase. Following this association, IL-1R-associated kinase phosphorylates tumor necrosis factor receptor-associated factor 6, which in turn attracts two more protein tyrosine kinases, transforming growth factor beta-activated kinase 1 (TAK-1)...

show abstract

“…In the HepG2 hepatoma cell line, which constitutively expresses IL-8 mRNA, AP-1 and PEA3 are shown to play important roles (15). In contrast, NF-B has been shown to be essential for expression of IL-8 in several types of cells, and TNF-␣ has been known as an activator of NF-B (29,30). In the present study, IL-8 production by TNF-␣ was inhibited by either Ad5IB or LY 294002.…”

Section: Discussionmentioning

confidence: 99%

“…However, hepatocytes are normally resistant to the cytotoxicity of TNF-␣. Administration of TNF-␣ alone does not induce hepatocyte apoptosis in mouse liver in vivo (25,29,31) or in cultured rat RALA (40) and human Hc (30) hepatocytes, suggesting that TNF-␣ also activates molecules that protect cells against apoptosis. For example, TNF-␣ transmits antiapoptotic signals via nuclear factor B (NF-B) and phosphatidylinositol 3-kinase (PI3K)/Akt.…”

mentioning

confidence: 99%

Tumor Necrosis Factor Alpha-Induced Interleukin-8 Production via NF-κB and Phosphatidylinositol 3-Kinase/Akt Pathways Inhibits Cell Apoptosis in Human Hepatocytes

Osawa¹,

Nagaki²,

Banno

et al. 2002

Infect Immun

Self Cite

View full text Add to dashboard Cite

show abstract

Possible involvement of reactive oxygen species in D‐galactosamine–induced sensitization against tumor necrosis factor‐α–induced hepatocyte apoptosis

Cited by 43 publications

References 45 publications

Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver†

Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver†

Role of Toll-Like Receptors in Changes in Gene Expression and NF-κB Activation in Mouse Hepatocytes Stimulated with Lipopolysaccharide

Tumor Necrosis Factor Alpha-Induced Interleukin-8 Production via NF-κB and Phosphatidylinositol 3-Kinase/Akt Pathways Inhibits Cell Apoptosis in Human Hepatocytes

Contact Info

Product

Resources

About