TLR4 and MD-2 form a heterodimer that recognizes LPS (lipopolysaccharide) from Gram-negative bacteria. Eritoran is an analog of LPS that antagonizes its activity by binding to the TLR4-MD-2 complex. We determined the structure of the full-length ectodomain of the mouse TLR4 and MD-2 complex. We also produced a series of hybrids of human TLR4 and hagfish VLR and determined their structures with ...

It remains unclear whether and how cardiomyocytes contribute to the inflammation in chronic heart failure (CHF). We recently reviewed the capacity of cardiomyocytes to initiate inflammation, by means of expressing certain immune receptors such as toll-like receptors (TLRs) that respond to pathogen- and damage-associated molecular patterns (PAMP and DAMP). Previous studies observed TLR4-mediated...

BACKGROUND Toll-like receptors (TLR) are a family of pattern recognition receptors that constitutes a major part of the innate immune system. The TLR4/(Myeloid differentiation factor 88 (MyD88) signaling pathway has been shown to have oncogenic effects. METHODS To demonstrate the role of TLR4/MyD88 signaling in ovarian epithelial cancers (OECs), we examined the expression of TLR4, MyD88 and n...

We investigated whether Toll-like receptor (TLR) 4 is at work in the human endometrium. The expression of TLR4 mRNA in endometrial epithelial cells (EECs) and stromal cells (ESCs) was detected by RT-PCR and in situ hybridization. Western blotting analysis revealed the TLR4 protein expression in both cell populations. Treatment of lipopolysaccharide (LPS), the actions of which are mediated throu...

BACKGROUND Toll-like receptors (TLRs) are expressed in immune cells and hepatocytes. We examined whether hepatic Toll-like receptor 4 (TLR4) is involved in the acute hepatic injury caused by the administration of lipopolysaccharide (LPS) (septic shock model). METHODS Wild type (WT), TLR4-deficient and chimera mice underwent myeloablative bone marrow transplantation to dissociate between TLR4 ...

The molecular determinants underpinning how hexaacylated lipid A and tetraacylated precursor lipid IVa activate Toll-like receptor 4 (TLR4) are well understood, but how activation is induced by other lipid A species is less clear. Species specificity studies have clarified how TLR4/MD-2 recognises different lipid A structures, for example tetraacylated lipid IVa requires direct electrostatic in...

Background: Male infertility refers to the inability of a male to achieve a pregnancy in a fertile female. The root of many causes of infertility is miscommunication between immune and reproductive system. Male reproductive system is very sensitive and vulnerable, infections can hinder maturation and movement of spermatozoa lead to impaired fertility.All species need an immediate reply to the m...

BACKGROUND Intact Toll-like receptor 4 (TLR4) has been identified in hepatic stellate cells (HSCs), the primary fibrogenic cell type in liver. Here, we investigated the impact of TLR4 signaling on the gene expression network of HSCs by comparing the transcriptomic changes between wild-type (JS1) and TLR4 knockout (JS2) murine HSCs in response to two TLR4 ligands, lipopolysacchride (LPS), or hig...

Toll-like receptor (TLR4) 4 is present in numerous cell types and serves as the first point of defense in the innate immune system. Single-nucleotide polymorphisms (SNPs) are present in a number TLR genes and have been associated with various infection and inflammation disorders. Asp299Gly and Thr399Ile, TLR4 SNPs, are associated with tumor progression. In the present study, cases of ovarian ca...

Abdominal Aortic Aneurysm (AAA) is a major cause of mortality and morbidity in men over 65 years of age. Male apolipoprotein E knockout (ApoE(-/-)) mice infused with angiotensin II (AngII) develop AAA. Although AngII stimulates both JAK/STAT and Toll-like receptor 4 (TLR4) signaling pathways, their involvement in AngII mediated AAA formation is unclear. Here we used the small molecule STAT3 inh...