TGF-beta inhibits lipopolysaccharide-stimulated activity of c-Jun N-terminal kinase in mouse macrophages.
Transforming growth factor-beta (TGF-beta) is a potent anti-inflammatory cytokine. Although this cytokine inhibits lipopolysaccharide (LPS)-mediated septic shock, the molecular mechanism of TGF-beta is not well known. Since recent studies showed that c-Jun N-terminal kinase (JNK), one of the mitogen-activated protein kinases, plays an important role in LPS signalling, we focused here on the inhibitory action of TGF-beta1 on LPS-stimulated JNK activity in mouse macrophages. TGF-beta1 inhibited LPS-stimulation of phosphorylated JNK1 and JNK2 and consequently of JNK activity in the cells. This JNK activity resulted in a decreased level of phosphorylated c-Jun protein. Using Western blotting, we also observed TGF-beta1 inhibition of newly synthesized c-Jun protein in LPS-stimulated cells. These results demonstrate that TGF-beta1 inhibits LPS-stimulated JNK activity in mouse macrophages. Also, our present study suggests a possible inhibitory mechanism of TGF-beta in signalling of LPS-induced inflammatory responses.
Imai
K
K
Department of Oral Microbiology, Meikai University School of Dentistry Keyakidai, Sakado City, Saitama, Japan.
Takeshita
A
A
Hanazawa
S
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases