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Infection and Immunity, July 2001, p. 4590-4599, Vol. 69, No. 7
INSERM U430, Hôpital Broussais, and
Université Pierre et Marie Curie, Paris, France
Received 20 September 2000/Returned for modification 19 January
2001/Accepted 26 March 2001
Toll-like receptors (TLRs) are involved in human monocyte
activation by lipopolysaccharide (LPS) and Staphylococcus
aureus Cowan (SAC), suggesting that gram-positive and
gram-negative bacteria may trigger similar intracellular events.
Treatment with specific kinase inhibitors prior to cell stimulation
dramatically decreased LPS-induced cytokine production. Blocking of the
p38 pathway prior to LPS stimulation decreased interleukin-1
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.7.4590-4599.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Gram-Positive and Gram-Negative Bacteria Do Not
Trigger Monocytic Cytokine Production through Similar
Intracellular Pathways
(IL-1
), IL-1ra, and tumor necrosis factor alpha (TNF-
)
production, whereas blocking of the ERK1/2 pathways inhibited IL-1
,
IL-1
, and IL-1ra but not TNF-
production. When cells were
stimulated by SAC, inhibition of the p38 pathway did not affect
cytokine production, whereas only IL-1
production was decreased in
the presence of ERK kinase inhibitor. We also demonstrated that
although LPS and SAC have been shown to bind to CD14 before
transmitting signals to TLR4 and TLR2, respectively, internalization of
CD14 occurred only in monocytes triggered by LPS. Pretreatment of the
cells with SB203580, U0126, or a mixture of both inhibitors did not
affect internalization of CD14. Altogether, these results suggest that TLR2 signaling does not involve p38 mitogen-activated protein kinase
signaling pathways, indicating that divergent pathways are triggered by
gram-positive and gram-negative bacteria, thereby inducing cytokine production.
*
Corresponding author. Mailing address: INSERM U430, 96 rue Didot, 75674 Paris Cedex, France. Phone: 33 1 43 95 95 67. Fax: 33 1 45 45 90 59. E-mail:
marie-paule.carreno{at}brs.ap-hop-paris.fr.
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