Low-molecular-weight hyaluronic acid induces nuclear factor-kappaB-dependent resistance against tumor necrosis factor alpha-mediated liver injury in mice.
Standard
Low-molecular-weight hyaluronic acid induces nuclear factor-kappaB-dependent resistance against tumor necrosis factor alpha-mediated liver injury in mice. / Wolf, D; Schümann, J; Koerber, K; Kiemer, A K; Vollmar, A M; Sass, G; Papadopoulos, T; Bang, R; Klein, S D; Brüne, B; Tiegs, Gisa.
In: HEPATOLOGY, Vol. 34, No. 3, 3, 2001, p. 535-547.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Low-molecular-weight hyaluronic acid induces nuclear factor-kappaB-dependent resistance against tumor necrosis factor alpha-mediated liver injury in mice.
AU - Wolf, D
AU - Schümann, J
AU - Koerber, K
AU - Kiemer, A K
AU - Vollmar, A M
AU - Sass, G
AU - Papadopoulos, T
AU - Bang, R
AU - Klein, S D
AU - Brüne, B
AU - Tiegs, Gisa
PY - 2001
Y1 - 2001
N2 - Liver resident NK1.1+ T cells are supposed to play a pivotal role in the onset of inflammatory liver injury in experimental mouse models such as concanavalin A (Con A)-induced hepatitis. These cells, expressing the adhesion receptor, CD44, are largely depleted from the liver by a single intravenous injection of low-molecular-weight fragments of hyaluronic acid (LMW-HA). Here, we report that LMW-HA pretreatment protected mice from liver injury in several models of T-cell- and macrophage-dependent, tumor necrosis factor alpha (TNF-alpha)-mediated inflammatory liver injury, i.e., from liver injury induced by either Con A or Pseudomonas exotoxin A (PEA) or PEA/lipopolysaccharide (LPS). Interestingly, apart from inhibition of cellular adhesion, pretreatment of mice with LMW-HA was also capable of preventing hepatocellular apoptosis and activation of caspase-3 induced by direct administration of recombinant murine (rmu) TNF-alpha to D-galactosamine (GalN)-sensitized mice. LMW-HA-induced hepatoprotection could be neutralized by pretreatment with the nuclear factor-kappaB (NF-kappaB) inhibitor, pyrrolidine dithiocarbamate (PDTC), demonstrating the involvement of NF-kappaB in the observed protective mechanism. Indeed, injection of LMW-HA rapidly induced the production of TNF-alpha by Kupffer cells and the translocation of NF-kappaB into hepatocellular nuclei. Both LMW-HA-induced TNF-alpha production and NF-kappaB translocation were blocked by pretreatment with PDTC. Our findings provide evidence for an unknown mechanism of LMW-HA-dependent protection from inflammatory liver disease, i.e., induction of TNF-alpha- and NF-kappaB-dependent cytoprotective proteins within the target parenchymal liver cells.
AB - Liver resident NK1.1+ T cells are supposed to play a pivotal role in the onset of inflammatory liver injury in experimental mouse models such as concanavalin A (Con A)-induced hepatitis. These cells, expressing the adhesion receptor, CD44, are largely depleted from the liver by a single intravenous injection of low-molecular-weight fragments of hyaluronic acid (LMW-HA). Here, we report that LMW-HA pretreatment protected mice from liver injury in several models of T-cell- and macrophage-dependent, tumor necrosis factor alpha (TNF-alpha)-mediated inflammatory liver injury, i.e., from liver injury induced by either Con A or Pseudomonas exotoxin A (PEA) or PEA/lipopolysaccharide (LPS). Interestingly, apart from inhibition of cellular adhesion, pretreatment of mice with LMW-HA was also capable of preventing hepatocellular apoptosis and activation of caspase-3 induced by direct administration of recombinant murine (rmu) TNF-alpha to D-galactosamine (GalN)-sensitized mice. LMW-HA-induced hepatoprotection could be neutralized by pretreatment with the nuclear factor-kappaB (NF-kappaB) inhibitor, pyrrolidine dithiocarbamate (PDTC), demonstrating the involvement of NF-kappaB in the observed protective mechanism. Indeed, injection of LMW-HA rapidly induced the production of TNF-alpha by Kupffer cells and the translocation of NF-kappaB into hepatocellular nuclei. Both LMW-HA-induced TNF-alpha production and NF-kappaB translocation were blocked by pretreatment with PDTC. Our findings provide evidence for an unknown mechanism of LMW-HA-dependent protection from inflammatory liver disease, i.e., induction of TNF-alpha- and NF-kappaB-dependent cytoprotective proteins within the target parenchymal liver cells.
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - CD4 Lymphocyte Count
KW - Molecular Weight
KW - Lymphocyte Count
KW - Concanavalin A/pharmacology
KW - Lipopolysaccharides/pharmacology
KW - ADP Ribose Transferases
KW - Antigens, CD44/analysis
KW - Bacterial Toxins
KW - Cell Death/drug effects
KW - Cytokines/blood
KW - Drug-Induced Liver Injury/pathology/prevention & control
KW - Exotoxins/pharmacology
KW - Hyaluronic Acid/chemistry/pharmacology
KW - Kupffer Cells/metabolism
KW - Liver/pathology
KW - Liver Failure/etiology/prevention & control
KW - Macrophages/physiology
KW - NF-kappa B/antagonists & inhibitors/physiology
KW - T-Lymphocytes/immunology/pathology/physiology
KW - Tumor Necrosis Factor-alpha
KW - Virulence Factors
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - CD4 Lymphocyte Count
KW - Molecular Weight
KW - Lymphocyte Count
KW - Concanavalin A/pharmacology
KW - Lipopolysaccharides/pharmacology
KW - ADP Ribose Transferases
KW - Antigens, CD44/analysis
KW - Bacterial Toxins
KW - Cell Death/drug effects
KW - Cytokines/blood
KW - Drug-Induced Liver Injury/pathology/prevention & control
KW - Exotoxins/pharmacology
KW - Hyaluronic Acid/chemistry/pharmacology
KW - Kupffer Cells/metabolism
KW - Liver/pathology
KW - Liver Failure/etiology/prevention & control
KW - Macrophages/physiology
KW - NF-kappa B/antagonists & inhibitors/physiology
KW - T-Lymphocytes/immunology/pathology/physiology
KW - Tumor Necrosis Factor-alpha
KW - Virulence Factors
M3 - SCORING: Journal article
VL - 34
SP - 535
EP - 547
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
IS - 3
M1 - 3
ER -