Suppression of tumour necrosis factor-αbySchizonepeta tenuifoliawater extract via inhibition of IκBαdegradation and Jun N-terminal kinase/stress-activated protein kinase activation

2010 ◽  
Vol 62 (8) ◽  
pp. 1069-1076 ◽  
Author(s):  
Hee Kang ◽  
Sang-Woo Han ◽  
Joung-Woo Hong ◽  
Nak-Won Sohn
1990 ◽  
Vol 267 (1) ◽  
pp. 91-98 ◽  
Author(s):  
M Kohno ◽  
N Nishizawa ◽  
M Tsujimoto ◽  
H Nomoto

Tumour necrosis factor (TNF) is a potent mitogen for some fibroblast cell lines. Here we have examined the TNF-mediated changes in protein phosphorylation in Swiss 3T3 and human FS-4 fibroblasts, and compared them with changes observed after the treatment of cells with other mitogens, such as platelet-derived growth factor (PDGF) and bombesin. TNF stimulated the rapid phosphorylation of two 41,000-Mr and two 43,000-Mr cytosol proteins on tyrosine, threonine and/or serine, as did PDGF, epidermal growth factor and fibroblast growth factor; the increased levels of this mitogen-induced protein-tyrosine phosphorylation correlated well with the extent of mitogen-induced DNA synthesis as determined by the percentage of labelled nuclei. In contrast, bombesin, which is an even better mitogen for Swiss 3T3 cells than TNF, stimulated the tyrosine phosphorylation of 41,000-Mr and 43,000-Mr proteins only to a limited extent. On the other hand, bombesin and PDGF stimulated the rapid serine phosphorylation of an 80,000-Mr acidic protein, a major substrate for protein kinase C; increased phosphorylation of the 80,000-Mr protein was not observed at all when cells were stimulated with TNF. These results suggest significant differences among the mitogenic signalling pathways of TNF, PDGF and bombesin as regards the involvement of protein kinases; the mitogenic signalling pathway of TNF involves the activation of tyrosine kinase, but not of protein kinase C, whereas bombesin seems to transduce its mitogenic signal mainly through the activation of protein kinase C, and the activation of both kinases seems to be involved in the mitogenic signalling pathway of PDGF.


2002 ◽  
Vol 366 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Ahmed A.A. MOHAMED ◽  
Orla J. JUPP ◽  
Helen M. ANDERSON ◽  
Alison F. LITTLEJOHN ◽  
Peter VANDENABEELE ◽  
...  

The activation of the extracellular signal-regulated kinases (ERKs) by tumour necrosis factor-α (TNF) receptors (TNFRs) is an integral part of the cytokine's pleiotropic cellular responses. Here we report differences in the caspase sensitivity and TNFR subtype activation of members of the ERK family. Inhibition in HeLa cells of caspase function by pharmacological inhibitors or the expression of CrmA (cytokine response modifier A), a viral modifier protein, blocks TNF-induced apoptosis or caspase-dependent protein kinase Cδ and poly(ADP-ribose) polymerase protein degradation. TNFR1- or TNFR2-stimulated c-Jun N-terminal kinase (JNK) activity was attenuated in cells in which caspase activity was inhibited either by pharmacological blockers or CrmA expression. Both TNFR1- and TNFR2-stimulated JNK activity was caspase-sensitive; however, only TNFR1 was capable of stimulating p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK activities. TNFR1-stimulated p42/44 MAPK and p38 MAPK activities were insensitive to pharmacological caspase inhibition or CrmA. These findings were supported when measuring TNF-induced cytosolic phospholipase A2 activation, which is a downstream target for MAPK and p38 MAPK. Profiling caspase enzymes activated by TNF in HeLa cells showed sequential caspase-8, −3, −7, −6 and −9 activation, with their inhibition characteristics suggesting a role for caspase-3 and/or caspase-6 in modulating JNK activity. Taken together these results show delineated ERK-activation pathways employed by TNFR subtypes.


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