PMID- 9106265
OWN - NLM
STAT- MEDLINE
DCOM- 19970724
LR  - 20190831
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 30
IP  - 4-5
DP  - 1997 Apr-May
TI  - Protein tyrosine kinase inhibitors decrease lipopolysaccharide-induced 
      proinflammatory cytokine production in mixed glia, microglia-enriched or 
      astrocyte-enriched cultures.
PG  - 491-7
AB  - Proinflammatory cytokines, tumor necrosis factor-alpha (TNF alpha), interleukin-1 
      (IL-1), and interleukin-6 (IL-6), produced by glial cells have been implicated in 
      the neuropathogenesis of various diseases. However, the signal transduction 
      pathway(s) for the production of these cytokines in glial cells are not well 
      understood. This study examined the effects of two potent protein tyrosine kinase 
      inhibitors, genistein and tyrphostin A25, on lipopolysaccharide (LPS)-induced 
      production of TNF alpha, IL-1 alpha, and IL-6 in mouse primary mixed glia, 
      microglia- or astrocyte-enriched cultures. LPS dose-dependently increased the 
      production of TNF alpha, IL-1 alpha, and IL-6 from the mixed glia cultures. 
      Genistein or tyrphostin A25 significantly inhibited the LPS-induced production of 
      these cytokines. The LPS-induced TNF alpha, IL-1 alpha, and IL-6 production in 
      microglia- or astrocyte-enriched cultures were also inhibited by tyrphostin A25. 
      These results demonstrate that protein tyrosine kinases are involved in the 
      signaling events of the LPS-induced production of TNF alpha, IL-1 alpha, or IL-6 
      in microglia or astrocytes, which may provide insights into therapeutic 
      interventions in the pathway for cytokine production in the brain.
FAU - Kong, L Y
AU  - Kong LY
AD  - Section of Neuropharmacology, National Institute of Environmental Health 
      Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
FAU - Lai, C
AU  - Lai C
FAU - Wilson, B C
AU  - Wilson BC
FAU - Simpson, J N
AU  - Simpson JN
FAU - Hong, J S
AU  - Hong JS
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Isoflavones)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitriles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tyrphostins)
RN  - 118409-58-8 (tyrphostin 25)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/enzymology/metabolism
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/*biosynthesis
MH  - Enzyme Inhibitors/*pharmacology
MH  - Genistein
MH  - Inflammation Mediators
MH  - Interleukin-6/biosynthesis
MH  - Isoflavones/*pharmacology
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - Microglia/drug effects/enzymology/metabolism
MH  - Neuroglia/drug effects/enzymology/*metabolism
MH  - Nitriles/*pharmacology
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - *Tyrphostins
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - 10.1016/s0197-0186(96)00086-1 [doi]
PST - ppublish
SO  - Neurochem Int. 1997 Apr-May;30(4-5):491-7. doi: 10.1016/s0197-0186(96)00086-1.