Hemin and a metabolic derivative coprohemin modulate the TLR4 pathway differently through different molecular targets:

Innate Immunity

MatteoPiazza¹ 

关键词: TLR4;    MD-2;    heme;    hemin;    coprohemin;   

DOI  :  10.1177/1753425910369020

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

Heme is a prosthetic group in a large number of essential proteins that have a pivotal role in oxygen transport, storage and electron shuttling. High amounts of free heme are associated with pathological states. Recently, it has been suggested that activation of Toll-like receptor 4 (TLR4) is one of the ways in which the ‘danger signal’ of free heme is detected. Here, we examine the biochemical basis of the modulation of the TLR4 pathway by hemin (iron(III)-protoporphyrin IX) and its metabolic, oxidated derivative coprohemin (iron(III)-coproporphyrin I). High concentrations of hemin (50 μM) triggered TLR4-mediated IL-8 production in the human HEK293/TLR4 cell line in the absence of the co-receptors CD14 and MD-2; the latter an essential co-receptor for TLR4 activation by endotoxin. Hemin and endotoxin have additive effects when co-administrated to HEK/TLR4 cells, suggesting that hemin and endotoxin activate TLR4 by different mechanisms. Coprohemin, in contrast to hemin, is unable to trigger TLR4-dependent...

【 授权许可】

CC BY