Dataset Information

Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.

ABSTRACT:

Aims

Aim was to elucidate the specific role of pattern recognition receptors in vascular dysfunction during polymicrobial sepsis (colon ascendens stent peritonitis, CASP).

Methods and results

Vascular contractility of C57BL/6 (wildtype) mice and mice deficient for Toll-like receptor 2/4/9 (TLR2-D, TLR4-D, TLR9-D) or CD14 (CD14-D) was measured 18 h following CASP. mRNA expression of pro- (Tumor Necrosis Factor-? (TNF?), Interleukin (IL)-1?, IL-6) and anti-inflammatory cytokines (IL-10) and of vascular inducible NO-Synthase (iNOS) was determined using RT-qPCR. Wildtype mice exhibited a significant loss of vascular contractility after CASP. This was aggravated in TLR2-D mice, blunted in TLR4-D animals and abolished in TLR9-D and CD14-D animals. TNF-? expression was significantly up-regulated after CASP in wildtype and TLR2-D animals, but not in mice deficient for TLR4, -9 or CD14. iNOS was significantly up-regulated in TLR2-D animals only. TLR2-D animals showed significantly higher levels of TLR4, -9 and CD14. Application of H154-ODN, a TLR9 antagonist, attenuated CASP-induced cytokine release and vascular dysfunction in wildtype mice.

Conclusions

Within our model, CD14 and TLR9 play a decisive role for the development of vascular dysfunction and thus can be effectively antagonized using H154-ODN. TLR2-D animals are more prone to polymicrobial sepsis, presumably due to up-regulation of TLR4, 9 and CD14.

SUBMITTER: Ehrentraut SF

PROVIDER: S-EPMC3436884 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.

Ehrentraut Stefan Felix SF Dörr Anne A Ehrentraut Heidi H Lohner Ralph R Lee Sun-Hee SH Hoeft Andreas A Baumgarten Georg G Knuefermann Pascal P Boehm Olaf O Meyer Rainer R

PloS one 20120907 9

<h4>Aims</h4>Aim was to elucidate the specific role of pattern recognition receptors in vascular dysfunction during polymicrobial sepsis (colon ascendens stent peritonitis, CASP).<h4>Methods and results</h4>Vascular contractility of C57BL/6 (wildtype) mice and mice deficient for Toll-like receptor 2/4/9 (TLR2-D, TLR4-D, TLR9-D) or CD14 (CD14-D) was measured 18 h following CASP. mRNA expression of pro- (Tumor Necrosis Factor-α (TNFα), Interleukin (IL)-1β, IL-6) and anti-inflammatory cytokines (IL ...[more]

PMID: 22970242

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Dataset Information

Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.

Aims

Methods and results

Conclusions

Publications

Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.

Similar Datasets

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