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01.12.2012 | Short Report | Ausgabe 1/2012 Open Access

Journal of Inflammation 1/2012

Stimulation of TLR4 by recombinant HSP70 requires structural integrity of the HSP70 protein itself

Zeitschrift:
Journal of Inflammation > Ausgabe 1/2012
Autoren:
Michael Luong, Yanyu Zhang, Tim Chamberlain, Tianhui Zhou, Jill F Wright, Ken Dower, J Perry Hall
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-9255-9-11) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

ML: conceived and performed experiments, analyzed data, and helped write the manuscript. YZ: conceived and performed experiments, analyzed data, and helped write the manuscript. TC: conceived and performed experiments, analyzed data, and helped write the manuscript. TZ: analyzed data and helped write the manuscript. JW: conceived experiments, analyzed data, and helped write the manuscript. KD: conceived and performed experiments, analyzed data, and helped write the manuscript. JPH: conceived and performed experiments, analyzed data, and helped write the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Toll-like receptor 4 (TLR4) is activated by bacterial endotoxin, a pathogen-associated molecular pattern (PAMP). It has been suggested that TLR4 can also be activated by damage-associated molecular pattern (DAMP) proteins such as HSP70. It remains a challenge to provide unequivocal evidence that DAMP proteins themselves play a role in TLR4 activation, as the DAMP proteins used are often contaminated with endotoxin and other TLR ligands introduced during protein expression and/or purification.

Results

Here we report that the activation of TLR4 on primary human macrophage cultures by recombinant HSP70 is not solely due to contaminating endotoxin. Polymyxin B pretreatment of HSP70 preparations to neutralize contaminating endotoxin caused significant reductions in the amount of TNF-α induced by the recombinant protein. However, digestion of HSP70 with Proteinase K-agarose beads also dramatically reduced the TNF-α response of macrophages to HSP70, while leaving levels of contaminating endotoxin largely unchanged relative to controls.

Conclusions

These results indicate that the stimulatory effect of recombinant HSP70 requires both the presence of endotoxin and structural integrity of the heat shock protein itself.
Zusatzmaterial
Authors’ original file for figure 1
12950_2011_228_MOESM1_ESM.pdf
Authors’ original file for figure 2
12950_2011_228_MOESM2_ESM.pdf
Literatur
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