Preconditioning with high mobility group box 1 (HMGB1) induces lipoteichoic acid (LTA) tolerance.

Preconditioning with high mobility group box 1 (HMGB1) induces lipoteichoic acid (LTA) tolerance.
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DOI:
10.1097/cji.0b013e3181dcd111
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发表时间:
2010-09
期刊:
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子:
--
通讯作者:
Aneja RK
Aneja RK
中科院分区:
其他
文献类型:
--
作者:
Robert SM;Sjodin H;Fink MP;Aneja RK

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High mobility group box chromosomal protein 1 (HMGB1) is a DNA binding protein that exhibits pro-inflammatory properties when present in the extracellular compartment. Putative receptors for HMGB1 include Toll-like receptor (TLR) 4, TLR2 and the receptor for advanced glycation end products (RAGE). We tested the hypothesis that extracellular HMGB1 can induce tolerance to the bacterial product, lipoteichoic acid (LTA). Pretreatment of human monocyte-like THP-1 cells with 1 μg/ml HMGB1 18 h before exposure to LTA (10 μg/ml) decreased secretion of TNF, NF-κB DNA-binding, and degradation of IκBα. Denaturation of HMGB1 with boiling water or co-incubation with anti-HMGB1 antibody abrogated the induction of tolerance to LTA. In contrast, co-incubation with polymyxin B failed to diminish HMGB1-induced tolerance to LTA. These findings support the view that the induction of LTA tolerance by HMGB1 was not due to LPS contamination. Bone marrow-derived macrophages obtained from C57Bl/6 wild-type and RAGE-deficient mice became LTA-tolerant following HMGB1 exposure ex vivo. We were unable to demonstrate LTA tolerance in TLR2 and TLR4-deficient macrophages, as they are hyporesponsive to LTA. These findings suggest that extracellular HMGB1 induces LTA tolerance, and RAGE receptor is not required for this induction.