TLR4 activation depends on the serum protein lipopolysaccharide (LPS)-binding protein, the co-receptor CD14 and myeloid differentiation protein-2 (MD-2) for bacterial recognition. Free heme can activate TLR4-mediated signaling and soluble CD14 has been found to be critical for the regulatory effects of heme.

2007年7月13日 · Heme induces ROS generation, neutrophil recruitment and HO-1 expression independently of TLR4. A, peritoneal macrophages from Tlr4 +/+ (C3H/HePas) or Tlr4 d/d (C3H/HeJ) mice were stimulated with heme (30 μ m) for 1 h. ROS were measured by flow cytometry, and results are representative of two different experiments.

2014年1月16日 · Heme/TLR4 signaling activates NF-κB and triggers vaso-occlusion through Weibel-Palade body degranulation and adhesion molecule expression. Treatment of sickle cell disease (SCD) is hampered by incomplete understanding of pathways linking hemolysis to vaso-occlusion. We investigated these pathways in transgenic sickle mice.

2023年10月26日 · We report the interaction of TLR4, MD2 and the TLR4-MD2 complex with heme and the consequences thereof by employing biochemical, spectroscopic, bioinformatic and physiologically relevant approaches. Heme binding occurs transiently through interaction with up to four HBMs in TLR4, two HBMs in MD2 and at least four HBMs in their complex.

2014年1月16日 · TLR4 (-/-) mice transplanted with TLR4 (+/+) sickle bone marrow exhibited no heme-induced vaso-occlusion. The TLR4 agonist lipopolysaccharide (LPS) activated ECs and triggered vaso-occlusion that was inhibited by TAK-242, linking hemolysis- and infection-induced vaso-occlusive crises to TLR4 signaling.

We report the interaction of TLR4, MD2 and the TLR4-MD2 complex with heme and the consequences thereof by employing biochemical, spectroscopic, bioinformatic and physiologically relevant approaches. Heme binding occurs transiently through interaction with up to four HBMs in TLR4, two HBMs in MD2 and at least four HBMs in their complex.

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).

2018年5月1日 · Heme is now recognized as an agonist for the Toll-like receptor-4 (TLR4) receptor. This study examined whether the TLR4 receptor mediates the nephrotoxicity of heme, specifically, the effects of heme on renal blood flow and inflammatory responses. We blocked TLR4 signaling by the specific antagonist TAK-242.

2020年8月26日 · TLR4 activation depends on the serum protein lipopolysaccharide (LPS)-binding protein, the co-receptor CD14 and myeloid differentiation protein-2 (MD-2) for bacterial recognition. Free heme can activate TLR4-mediated signaling and soluble CD14 has been found to be critical for the regulatory effects of heme.

2019年6月1日 · In the current study we hypothesized that alterations in the levels of intracellular labile heme in macrophages stimulated by lipopolysaccharide (LPS), a prototypical pro-inflammatory Toll-like receptor (TLR)4 agonist, are responsible for BACH1-dependent HO-1 …