PMID- 9568551
OWN - NLM
STAT- MEDLINE
DCOM- 19980612
LR  - 20190909
IS  - 0192-0561 (Print)
IS  - 0192-0561 (Linking)
VI  - 19
IP  - 8
DP  - 1997 Aug
TI  - Differential effects on TNF alpha production by pharmacological agents with 
      varying molecular sites of action.
PG  - 451-62
AB  - This study describes the activation conditions for tumor necrosis factor-alpha 
      (TNF alpha) production in myelomonocytic U937 cells and human primary peripheral 
      blood monocytes in response to lipopolysaccharide (LPS) and/or phorbol 
      12-myristate 13-acetate (PMA). PMA itself induced only low levels of TNF alpha 
      production with delayed kinetics (e.g. 0.758 +/- 0.128 ng/ml from U937 cells 
      after 48 h) while LPS induced greater levels of TNF alpha production in less time 
      (e.g. 2.083 +/- 0.96 ng/ml from monocytes in 24 h). Pharmacological agents with 
      various molecular sites of action were used to validate the two systems, with the 
      protein serine-threonine kinase inhibitors staurosporine and Ro-31-8220, the 
      protein tyrosine kinase inhibitor herbimycin A (HBA) and dexamethasone exhibiting 
      the greatest potency (IC50S 5-350 nM). In contrast to the effect on TNF alpha 
      production, PMA induced strong phosphorylation/activation of p42/p44mapk in 
      monocytes by 10 min determined in a mobility shift assay, while LPS was a weaker 
      inducer. Additionally, staurosporine (to LPS and PMA) and HBA (to LPS only) 
      inhibited the activation of these mitogen-activated protein kinase (MAPK) 
      isoforms at doses 10-100 fold higher than those required to inhibit maximal TNF 
      alpha production. These data indicate the involvement of the p42/p44mapk 
      signalling pathway in LPS-induced pro-inflammatory cytokine production but 
      suggest that other signalling pathways are also implicated in this phenomenon.
FAU - Mander, T
AU  - Mander T
AD  - Xenova Ltd, Slough, Berkshire, England.
FAU - Hill, S
AU  - Hill S
FAU - Hughes, A
AU  - Hughes A
FAU - Rawlins, P
AU  - Rawlins P
FAU - Clark, C
AU  - Clark C
FAU - Gammon, G
AU  - Gammon G
FAU - Foxwell, B
AU  - Foxwell B
FAU - Moore, M
AU  - Moore M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Int J Immunopharmacol
JT  - International journal of immunopharmacology
JID - 7904799
RN  - 0 (Benzoquinones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Quinones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 1W306TDA6S (Rifabutin)
RN  - 207137-56-2 (Interleukin-4)
RN  - 70563-58-5 (herbimycin)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - H88EPA0A3N (Staurosporine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Benzoquinones
MH  - Binding Sites
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism/physiology
MH  - Dexamethasone/pharmacology
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Interleukin-10/pharmacology
MH  - Interleukin-4/pharmacology
MH  - Lactams, Macrocyclic
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphoma, Large B-Cell, Diffuse/enzymology/metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism/physiology
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Monocytes/*drug effects/enzymology/*metabolism
MH  - Quinones/pharmacology
MH  - Rifabutin/analogs & derivatives
MH  - Signal Transduction/drug effects/physiology
MH  - Staurosporine/pharmacology
MH  - Structure-Activity Relationship
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1997/08/01 00:00
MHDA- 1998/05/06 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1998/05/06 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
AID - S019205619700088X [pii]
AID - 10.1016/s0192-0561(97)00088-x [doi]
PST - ppublish
SO  - Int J Immunopharmacol. 1997 Aug;19(8):451-62. doi: 10.1016/s0192-0561(97)00088-x.