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Regulation of Kupffer Cell TNF Gene Expression During Experimental Acute Pancreatitis: The Role of p38-MAPK, ERK1/2, SAPK/JNK, and NF-κB
- Source :
-
Journal of Gastrointestinal Surgery . Jan2003, Vol. 7 Issue 1, p20-25. 6p. - Publication Year :
- 2003
-
Abstract
- We have demonstrated that Kupffer cell–derived tumor necrosis factor (TNF) mediates pancreatitis-associated liver injury. The aim of this study was to determine the role of p38 mitogen-activated protein kinase (MAPK), extracellular stress-related kinase 1/2 (ERK1/2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and nuclear factor–κB (NF-κB) in TNF gene expression within Kupffer cells. TNF and TNF-mRNA were measured in rat livers perfused with elastase. TNF, TNF-mRNA, NF-κB activation, and phosphorylated p38-MAPK, SAPK/JNK, and ERK1/2 were determined in Kupffer cells treated with elastase. Elastase increased TNF and upregulated TNF-mRNA in livers (P<0.03) and Kupffer cells (P<0.001). Phosphorylated p38-MAPK, SAPK/JNK, and ERK1/2 and activated NF-κB were detected in Kupffer cells at 7 minutes; at 60 minutes, TNF-mRNA peaked and NF-κB returned to baseline, whereas all three kinases remained activated. Gadolinium inhibited elastase-induced upregulation of TNF-mRNA (P < 0.001), TNF production (P<0.001), and attenuated SAPK/JNK, as well as ERK1/2, but not p38-MAPK. Both UO126 and SB203580 significantly inhibited elastase-induced upregulation of TNF-mRNA and TNF production (P<0.001), but only UO126 inhibited activation of NF-κB. It was concluded that pretranscriptional regulation of TNF gene expression in Kupffer cells follows an orderly activation of p38-MAPK, ERK1/2, and SAPK/JNK that may not converge on NF-κB. The seemingly limited duration of NF-κB activation may be important in “switching off” the cytokine cascade during acute pancreatitis. ( J Gastrointest Surg 2003;7:20–25.) [Copyright &y& Elsevier]
- Subjects :
- *KUPFFER cells
*CELLULAR control mechanisms
*LIVER injuries
*PROTEIN kinases
*RNA metabolism
*ANIMAL experimentation
*BIOCHEMISTRY
*CELL culture
*CHEMICAL elements
*COMPARATIVE studies
*ELECTROPHORESIS
*GENES
*IMMUNOBLOTTING
*MACROPHAGES
*PHENOMENOLOGY
*RESEARCH methodology
*MEDICAL cooperation
*PANCREATITIS
*POLYMERASE chain reaction
*PROTEOLYTIC enzymes
*RATS
*RESEARCH
*TRANSFERASES
*TUMOR necrosis factors
*DNA-binding proteins
*EVALUATION research
*REVERSE transcriptase polymerase chain reaction
*ACUTE diseases
Subjects
Details
- Language :
- English
- ISSN :
- 1091255X
- Volume :
- 7
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Gastrointestinal Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 9142296
- Full Text :
- https://doi.org/10.1016/S1091-255X(02)00053-7