TNF-alpha induction by Pseudomonas aeruginosa lipopolysaccharide or slime-glycolipoprotein in human monocytes is regulated at the level of Mitogen-activated Protein Kinase activity: a distinct role of Toll-like receptor 2 and 4.

Abstract:

:TNF-alpha production has a central role in the development and progression of Pseudomonas aeruginosa septic shock. We have previously shown that P. aeruginosa slime-glycolipoprotein (slime-GLP) is the most potent stimulant compared to P. aeruginosa lipopolysaccharide (LPS), for TNF-alpha production and NF-kB activation in human monocytes. Herein, we show that secretion of TNF-alpha by fresh human monocytes, induced by P. aeruginosa slime-GLP, LPS or viable bacteria, was paralleled by phosphorylation and/or activation of Mitogen-activated Protein Kinases (MAPKs) ERK1/2, p38 as well as c-Jun NH(2)-terminal kinase. TNF-alpha levels were significantly reduced by ERK1/2 inhibitor (PD98059), or p38 inhibitor (SB203580). Combination of both inhibitors almost abolished TNF-alpha induction. Pseudomonas aeruginosa slime-GLP differed from the P. aeruginosa-LPS only regarding the strength of p38 and ERK1/2 activation, with slime-GLP leading to a stronger activation of p38 and ERK1/2. Involvement of TLR2 and TLR4 for phosphorylation of p38 and ERK1/2 was shown using specific blocking anti-TLR2 and anti-TLR4 antibodies. Activation of both p38 and ERK1/2 induced by P. aeruginosa slime-GLP was dramatically reduced in the presence of anti-TLR2 and to a lesser degree in the presence of anti-TLR4, whereas the P. aeruginosa-LPS-induced stimulation was inhibited only in the presence of anti-TLR4. Our data show that P. aeruginosa viable bacteria, through slime-GLP, stimulate specific members of the MAPKs more efficiently than the P. aeruginosa-LPS, involving mainly TLR2.

journal_name

Scand J Immunol

authors

Lagoumintzis G,Xaplanteri P,Dimitracopoulos G,Paliogianni F

doi

10.1111/j.1365-3083.2007.02053.x

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

193-203

issue

2

eissn

0300-9475

issn

1365-3083

pii

SJI2053

journal_volume

67

pub_type

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