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Lipopolysaccharide and pneumococcal cell wall components activate the mitogen activated protein kinases (MAPK) erk-1, erk- 2, and p38 in astrocytes

Item Type:Article
Title:Lipopolysaccharide and pneumococcal cell wall components activate the mitogen activated protein kinases (MAPK) erk-1, erk- 2, and p38 in astrocytes
Creators Name:Schumann, R.R. and Pfeil, D. and Freyer, D. and Buerger, W. and Lamping, N. and Kirschning, C.J. and Goebel, U.B. and Weber, J.R.
Abstract:Cell wall compounds of gram-positive bacteria are capable of inducing the biosynthesis of proinflammatory cytokines in CNS cells in a similar way as lipopolysaccharide (LPS) of gram-negative bacteria does. Astrocytes, which lack the CD14 LPS receptor, have also been shown to respond to LPS-stimulation by increased cytokine synthesis. However, almost nothing is known about signaling steps involved in this process. We have therefore examined signaling events in primary cultures of rat astrocytes and the human astrocytoma cell line U373MG, brought about by LPS and pneumococcal cell walls (PCW). Of particular interest to us was the tyrosine phosphorylation patterns and activation states of three members of the mitogen activated protein kinase (MAPK) family, i.e., extracellular signal-regulated protein kinase (erk)-1, erk-2, and the recently identified p38. We show that LPS and PCW initiate tyrosine phosphorylation and activation of erk-1, erk-2, and p38 in a dose-dependent fashion. Inhibitors of tyrosine phosphorylation were able to alleviate this effect and also blocked cytokine production of astrocytes. Both, LPS- and PCW-induced responses of astrocytic cells required the presence of soluble CD14 (sCD14) present in serum. Unraveling the signaling steps induced by bacterial compounds in cells of the CNS may potentially help to elucidate the pathomechanisms of meningitis and central nervous complications of sepsis and may offer options for novel treatment strategies.
Keywords:Meningitis, Astrocytes, LPS, Pneumococci, Signal Transduction, MAP Kinases, Animals, Rats
Source:Glia
ISSN:0894-1491
Publisher:Wiley (U.S.A.)
Volume:22
Number:3
Page Range:295-305
Date:1 March 1998
Official Publication:https://doi.org/10.1002/(SICI)1098-1136(199803)22:3<295::AID-GLIA8>3.0.CO;2-4
PubMed:View item in PubMed

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