Search results for "TLR4"

EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-κB Activation

2005

Abstract The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of the cytokine IL-27 that controls Th cell development. However, its regulated expression in DCs is poorly understood. In the present study we demonstrate that EBI3 is expressed in splenic CD8−, CD8+, and plasmacytoid DC subsets and is induced upon TLR signaling. Cloning and functional analysis of the EBI3 promoter using in vivo footprinting and mutagenesis showed that stimulation via TLR2, TLR4, and TLR9 transactivated the promoter in primary DCs via NF-κB and Ets binding sites at −90 and −73 bp upstream of the transcriptional start site, respectively. Furthermore, we observed that NF-κB p50/p65 and PU.1…

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4…

2021

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), a…

Role of TLR Polymorphisms in Aging and Age-Related Diseases

2017

Innate immunity provides the first line of host defense against infection by recognizing and killing microbes, and simultaneously activating an instructive immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition, and they mainly function by detecting exogenous pathogen-associated molecular patterns. Recognition of their ligands actives signaling ways, which culminate in evocating acute host responses, involved in killing pathogens. Here, we describe the involvement of TLR4 polymorphisms in aging, and particularly in immunosenescence and age-related diseases, suggesting the crucial role of molecules of innate immunity in the pathophysiology of these…

Innate Sensing by Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis

2018

MyD88, an adaptor molecule downstream of innate pathways, plays a significant tumor-promoting role in sporadic intestinal carcinogenesis, which is dependent on its function in the stroma. Here, we show that deletion of MyD88 in intestinal mesenchymal cells (IMCs) significantly reduces Apc-mediated intestinal tumorigenesis. This phenotype is associated with decreased epithelial cell proliferation, altered inflammatory and tumorigenic immune cell infiltration, and modified gene expression similar to complete MyD88 knockout mice. Genetic deletion of TLR4, but not IL1R, in IMCs led to altered molecular profiles and reduction of intestinal tumors similar to the MyD88 deficiency. Ex vivo analysis…

Candida albicans: to be or not to be recognized by TLR4? Response to “Both TLR2 and TLR4 are involved in the recognition of Candida albicans” by M.G.…

2006

Role of TLR Polymorphisms in Immunosenescence

2009

Innate immunity provides a first line of host defense against infection through microbial recognition and killing while simultaneously activating a clonotypic immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of pathogen-associated molecular patterns (PAMPs) that do not exist in the host. The different members of TLRs recognize several PAMPs, such as peptidoglycan for TLR2, lipopolysaccharide (LPS) for TLR4, flagellin for TLR5, and CpGDNA-repeats for TLR9. Several endogenous ligands of various TLRs have been also identified in the host. In this chapter, we describe the involvement of TLR-4 polymorphisms in imm…

Mechanisms of Synergy Between Toll-Like Receptor 4 and Triggering Receptor Expressed on Myeloid Cells-1 in Human Neutrophils

2008

Abstract The triggering receptor expressed on myeloid cells 1 (TREM-1) is an important player in the innate inflammatory response to microbial infections. Activation and expression of TREM-1 by polymorphonuclear neutrophils (PMN) occurs in concert with Toll-like receptors (TLR) such as TLR4 for bacterial lipopolysaccharide. However, it is currently unclear how this is mediated on a molecular level. Using pharmacologic inhibitors and western blot analysis we demonstrate that phosphatidyl inositide 3-kinase, phospholipase C and the mitogen activated kinase p38 are essential for the TREM-1 and TLR4 mediated respiratory burst of human PMN. The down stream phosphorylation of protein kinase B and…

Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID…

2021

AbstractOvershooting immune reactions can occur during inflammatory responses that accompany severe infections, such as COVID-19. Cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen and nitrogen species can generate positive feedback loops of inflammation, leading to long-term complications such as vascular endothelialitis, thrombosis, endothelial dysfunction, neurological impairments, and chronic fatigue. Dexamethasone can limit inflammation by inhibiting the activation of pro-inflammatory transcription factors. High dose dexamethasone, however, has undesirable side effects. Here, we show that Ceylon cinnamon and its major compound cinnamaldehyde can mitigate infla…

Toll-like receptors play a crucial part in the pathophysiological activity of antiphospholipid antibodies

2011

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis, recurrent fetal loss and the presence of a variety of antiphospholipid antibodies (aPL), directed to phospholipids like Cardiolipin and phospholipid binding proteins like β2-glycoprotein I. Till date, the pathophysiological processes underlying these thrombotic events were still not fully understood. Recent data support the idea that the aPL might act via enhanced cytokine release due to activation of certain Toll-like receptors. The investigation of some of those mechanisms in more detail enlightens the involvement of the intracellular receptors TLR7 and TLR8 in a central point. Using patients…

Penicillium lanoso-viride AMP dezamināzi atpazīstošo receptoru klāsta detektēšana perifēro asiņu mononukleārajās šūnās

2016

Šajā darbā salīdzināta Penicillium lanoso-viride sintezētās AMPD un citu sēņu izcelsmes imūnmodulatoru un standartvielu iedarbība uz iekaisuma reakcijās iesaistītu molekulu gēnu ekspresiju un sekrēciju asins imūnsistēmas šūnās, un, balstoties uz rezultātos iegūto informāciju, veikta AMPD atpazīstošo PRR analīze. Ar RT-PCR metodi veiktās analīzes uzrāda, ka AMPD stimulētās asins imūnajās šūnās ir paaugstināta iekaisuma citokīnu, kā arī TLR4 signālceļā iesaistīto molekulu gēnu ekspresija, kas norāda uz tās iekaisumu veicinošo ietekmi. Ar receptoru bloķēšanas un ELISA proteīnu koncentrācijas noteikšanas metodes palīdzību noskaidrots, ka AMPD savu imūnmodulatoro darbību asins mononukleārajās šū…