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Chun Wai Liew, Tiffany Phuong, Carli B Jones, Samantha Evans, Justin Hoot, Kendall Weedling, Damarcus Ingram, Stacy Nganga, Robert A Kurt
We developed an agent-based model to simulate a signaling cascade which allowed us to focus on the behavior of each class of agents independently of the other classes except when they were in physical contact. A critical piece was the ratio of the populations of agents that interact with one another, not their absolute values. This ratio reflects the effects of the density of each agent in the biological cascade as well as their size and velocity. Although the system can be used for any signaling cascade in any cell type, to validate the system we modeled Toll-like receptor (TLR) signaling in two very different types of cells; tumor cells and white blood cells...
February 1, 2018: Computers in Biology and Medicine
Yan Wang, Jingxia Zhao, Tingting Di, Mingxing Wang, Zhitong Ruan, Lu Zhang, Xiangjiang Xie, Yujiao Meng, Yan Lin, Xin Liu, Ning Wang, Ping Li
β,β-dimethylacryloyl alkannin (DMA) is a key component of Lithospermum and possesses good efficacy for treating psoriasis. DMA inhibits activated dendritic cells (DCs), but the mechanism is unknown. Therefore, this study aimed to explore the modulation of the TLR7/8 pathway by DMA in psoriasis-activated DCs. Models of psoriasis-like skin lesions were established using BALB/c mice; 8 mice were treated with DMA (2.5mg/kg). Bone marrow cells were isolated and induced into DCs using R848, a TLR7/8 agonist. Splenic CD11c+ cells were detected by flow cytometry...
November 2016: International Immunopharmacology
Fatemeh Moheimani, Alan C-Y Hsu, Andrew T Reid, Teresa Williams, Anthony Kicic, Stephen M Stick, Philip M Hansbro, Peter A B Wark, Darryl A Knight
Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium...
2016: Respiratory Research
Hao Zhou, Minjia Yu, Junjie Zhao, Bradley N Martin, Sanjoy Roychowdhury, Megan R McMullen, Emily Wang, Paul L Fox, Sho Yamasaki, Laura E Nagy, Xiaoxia Li
Lipopolysaccharide (LPS)-mediated activation of Toll-like receptors (TLRs) in hepatic macrophages and injury to hepatocytes are major contributors to the pathogenesis of alcoholic liver disease. However, the mechanisms by which TLR-dependent inflammatory responses and alcohol-induced hepatocellular damage coordinately lead to alcoholic liver disease are not completely understood. In this study, we found that mice deficient in interleukin-1 receptor-associated kinase M (IRAKM), a proximal TLR pathway molecule typically associated with inhibition of TLR signaling, were actually protected from chronic ethanol-induced liver injury...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Anna González-Rascón, Verónica Mata-Haro
MicroRNAs (miRNAs) are similar in importance to transcription factors and critical to confer accuracy and robustness in gene expression programs and consequently, have emerged as controllers of the immune response. On the other hand, probiotic influence over immune responses against a wide spectrum of health conditions are widely studied but the mechanism for this modulation has not yet completely elucidated. One proposed mechanism involves the receptor-mediated interaction of dendritic cells with components of the cellular membrane and/or secreted peptides of probiotics ending with the production of cytokines...
2015: MicroRNA
Jaume Carrasco-Colom, Iolanda Jordan, Laia Alsina, Juan-José Garcia-Garcia, Francisco José Cambra-Lasaosa, María Anunciación Martín-Mateos, Manel Juan, Carmen Muñoz-Almagro
BACKGROUND: Severe invasive pneumococcal disease (SIPD) has high morbidity and mortality, conditioned by pneumococcus and host factors, such as Toll-like receptors and their Toll-IL1R common signaling pathway. The objectives of this study are (1) to correlate single nucleotide polymorphisms (SNPs) involved in some Toll-IL1R signaling pathway proteins (IRAK1, IRAK4, IRAKM and MyD88) with SIPD by comparing patients versus healthy controls. (2) To determine whether these SNPs influence SIPD outcome...
September 2015: Pediatric Infectious Disease Journal
Shasha Zheng, Clara Abraham
Regulation of microbially induced cytokine secretion is critical in intestinal immune homeostasis. NOD2, the Crohn's disease-associated bacterial peptidoglycan sensor, activates the NF-κB pathway. After chronic NOD2 stimulation in human macrophages, cytokine secretion is significantly attenuated, similar to the situation in the intestinal environment. We find that NF-κB1 (p105/p50) expression is upregulated with chronic NOD2 stimulation and is required for attenuation of cytokine secretion in vitro in human macrophages and in vivo in mice...
December 2013: Molecular and Cellular Biology
P Xue, M Zheng, Z Diao, L Shen, M Liu, P Gong, H Sun, Y Hu
Among miRNAs, miR-155 is a known regulator of immune system. Accumulating studies have revealed the connections between miR-155 and activator protein 1 (AP-1)/nuclear factor (NF)-κB. However, miR-155*, a miR-155 paralog, has so far been less studied. Here we demonstrated that miR-155*, induced by lipopolysaccharide (LPS) in an AP-1/NF-κB dependent manner, played a positive feedback role in AP-1/NF-κB pathway via targeting interleukin-1 receptor-associated kinase M (IRAKM) and NF-κB inhibitor interacting Ras-like 1 (NKIRAS1) in trophoblasts...
August 2013: Placenta
Vijayakumar Gosu, Shaherin Basith, Prasannavenkatesh Durai, Sangdun Choi
The interleukin-1 receptor-associated kinase (IRAK) family comprises critical signaling mediators of the TLR/IL-1R signaling pathways. IRAKs are Ser/Thr kinases. There are 4 members in the vertebrate genome (IRAK1, IRAK2, IRAKM, and IRAK4) and an IRAK homolog, Pelle, in insects. IRAK family members are highly conserved in vertebrates, but the evolutionary relationship between IRAKs in vertebrates and insects is not clear. To investigate the evolutionary history and functional divergence of IRAK members, we performed extensive bioinformatics analysis...
2012: PloS One
Haibo Zhou, Xinfang Huang, Huijuan Cui, Xiaobing Luo, Yuanjia Tang, Shunle Chen, Li Wu, Nan Shen
The recent discovery of microRNAs (miRNAs) has revealed a new layer of gene expression regulation, affecting the immune system. Here, we identify their roles in regulating human plasmacytoid dendritic cell (PDC) activation. miRNA profiling showed the significantly differential expression of 19 miRNAs in PDCs after Toll-like receptor 7 (TLR7) stimulation, among which miR-155* and miR-155 were the most highly induced. Although they were processed from a single precursor and were both induced by TLR7 through the c-Jun N-terminal kinase pathway, miR-155* and miR-155 had opposite effects on the regulation of type I interferon production by PDC...
December 23, 2010: Blood
K M Lammers, S Ouburg, S A Morré, J B A Crusius, P Gionchett, F Rizzello, C Morselli, E Caramelli, R Conte, G Poggioli, M Campieri, A S Peña
AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls...
December 14, 2005: World Journal of Gastroenterology: WJG
N Ireland, M Kalkoff, R T Cursons, J W Sleigh
The aim of this longitudinal observational study was to investigate and describe the spectrum of messenger ribonucleic acid (mRNA) expression of multiple inflammatory markers in circulating leukocytes after major orthopaedic surgery. We studied ten elective arthroplasty patients perioperatively on the orthopaedic ward, and eight healthy volunteers for a comparison group. Venous blood specimens were collected preoperatively, and 6, and 24 hours postoperatively, together with 6- and 24-hour postoperative wound drain specimens...
April 2004: Anaesthesia and Intensive Care
Xiaoxia Li, Jinzhong Qin
Toll-like receptors (TLRs) belong to the Toll-interleukin 1 receptor superfamily, which is defined by a common intracellular Toll-IL-1 receptor (TIR) domain. A group of TIR domain containing adaptors (MyD88, TIRAP, TRIF and TRAM), are differentially recruited to the Toll-IL-1 receptors, contributing to the specificity of signaling. The IL-1 mediated signaling pathway serves as a "prototype" for other family members. Genetic and biochemical studies reveal that IL-1R uses adaptor molecule MyD88 to mediate a very complex pathway, involving a cascade of kinases organized by multiple adapter molecules into signaling complexes, leading to activation of the transcription factor NFkappaB...
April 2005: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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