How infection precipitates depressed contractility is incompletely understood but may involve the immune, nervous, and endocrine systems as well as the heart itself. In this study, we examined the role of Toll-like receptor 4 (TLR4) in LPS-induced myocardial contractile depression. Eighteen hours following endotoxin challenge, we compared contractile responses in hearts from wild-type (WT) and ...

Abstract Adhesion and degranulation–promoting adapter protein (ADAP), originally identified as an essential adaptor molecule in TCR signaling T cell adhesion, has emerged a critical regulator innate immune cells such macrophages; however, its role macrophage polarization inflammatory responses remains unknown. In this study, we show that ADAP plays TLR4-mediated mouse via modulation of STAT3 ac...

TLR4 is crucial for macrophage responses to LPS. It is less clear whether TLR4 may also transduce signals from host factors, and if so, with what consequences. Immortalized bone marrow-derived macrophage cell lines, termed T4Cr and T4ko, were established from TLR4null strains, C57BL/10ScNCr and TLR4 knockout mice, respectively. Multiple transfections and selections were conducted to stably intr...

signaling amp-activated protein kinase (ampk), an energy sensing enzyme, has been implicated in controlling inflammation. in this study we investigated whether activation of ampk by metformin could protect the lung from lipopolysaccharide (lps)-induced acute injury by inhibitingng tlr4 pathway. male wistar rats were randomly divided into 3 groups (n=6): control group received normal saline (0.5...

Asp(299)Gly (D299G) and, to a lesser extent, Thr(399)Ile (T399I) TLR4 polymorphisms have been associated with gram-negative sepsis and other infectious diseases, but the mechanisms by which they affect TLR4 signaling are unclear. In this study, we determined the impact of the D299G and T399I polymorphisms on TLR4 expression, interactions with myeloid differentiation factor 2 (MD2), LPS binding,...

Neonatal maternal separation (MS) is a major early life stress that increases the risk of emotional disorders, visceral pain perception and other brain dysfunction. Elevation of toll-like receptor 4 (TLR4) signaling in the paraventricular nucleus (PVN) precipitates early life colorectal distension (CRD)-induced visceral hypersensitivity and pain in adulthood. The present study aimed to investig...

Endotoxin-mediated ileus is poorly understood. Our objective was to mechanistically investigate the role of cell-specific TLR4 expression/signaling in causing gastrointestinal dysmotility. TLR4 chimeras and CSF-1-dependent macrophage-deficient mice were subjected to i.p. ultrapure (UP)-LPS (5 mg/kg). At 6 h, gastric emptying and gastrointestinal transit assessed in vivo motility, and jejunal ci...

objective(s): high mobility group box1 (hmgb1) is a nonhistone, dna-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. the aim of this study was to explore whether hmgb1 stimulation can up-regulate the expression of toll-like receptor 2 (tlr2) and toll-like receptor 4 (tlr4) on macrophages from p...