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https://www.readbyqxmd.com/read/28671993/epithelial-cells-detect-functional-type-iii-secretion-system-of-enteropathogenic-escherichia-coli-through-a-novel-nf-%C3%AE%C2%BAb-signaling-pathway
#1
Yael Litvak, Shir Sharon, Meirav Hyams, Li Zhang, Simi Kobi, Naama Katsowich, Shira Dishon, Gabriel Nussbaum, Na Dong, Feng Shao, Ilan Rosenshine
Enteropathogenic Escherichia coli (EPEC), a common cause of infant diarrhea, is associated with high risk of mortality in developing countries. The primary niche of infecting EPEC is the apical surface of intestinal epithelial cells. EPEC employs a type three secretion system (TTSS) to inject the host cells with dozens of effector proteins, which facilitate attachment to these cells and successful colonization. Here we show that EPEC elicit strong NF-κB activation in infected host cells. Furthermore, the data indicate that active, pore-forming TTSS per se is necessary and sufficient for this NF-κB activation, regardless of any specific effector or protein translocation...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28655577/nod1-is-the-innate-immune-receptor-for-ie-dap-and-can-activate-nf-%C3%AE%C2%BAb-pathway-in-teleost-fish
#2
Dekun Bi, Yunhang Gao, Qing Chu, Junxia Cui, Tianjun Xu
The innate immune system is the first line for organisms defense against microbial infection, and NOD-like receptors (NLRs) protein family is an important member of innate immunity effector molecules. It has been proved that NLRs are located in the endochylema and can senses of microbial products. NOD1 is one of the representatives of this family, it has been proved that in mammals, NOD1 can distinguish a specific muropeptide (G-d-glutamyl-meso-diaminopimelic acid, iE-DAP) which was derived from bacterial peptidoglycans...
June 24, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28652394/lack-of-both-nucleotide-binding-oligomerization-domain-containing-proteins-1-and-2-primes-t-cells-for-activation-induced-cell-death
#3
Sashi G Kasimsetty, Alana A Shigeoka, Andrew A Scheinok, Amanda L Gavin, Richard J Ulevitch, Dianne B McKay
Nucleotide-binding oligomerization domain (Nod)-containing proteins Nod1 and Nod2 play important roles in the innate immune response to pathogenic microbes, but mounting data suggest these pattern recognition receptors might also play key roles in adaptive immune responses. Targeting Nod1 and Nod2 signaling pathways in T cells is likely to provide a new strategy to modify inflammation in a variety of disease states, particularly those that depend on Ag-induced T cell activation. To better understand how Nod1 and Nod2 proteins contribute to adaptive immunity, this study investigated their role in alloantigen-induced T cell activation and asked whether their absence might impact in vivo alloresponses using a severe acute graft versus host disease model...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28651476/molecular-mechanisms-of-intrauterine-growth-restriction
#4
Rao Gurugubelli Krishna, B Vishnu Bhat
Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFβ causes the placental apoptosis and altered expression of TGFβ due to hyper alimentation causes impairment of lung function...
July 10, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28640392/calcineurin-inhibitors-exacerbate-coronary-arteritis-via-the-myd88-signaling-pathway-in-a-murine-model-of-kawasaki-disease
#5
Kenji Murata, Yoshitomo Motomura, Tamami Tanaka, Shunsuke Kanno, Takahisa Yano, Mitsuho Onimaru, Atsushi Shimoyama, Hisanori Nishio, Yasunari Sakai, Masatsugu Oh-Hora, Hiromitsu Hara, Koichi Fukase, Hidetoshi Takada, Satohiro Masuda, Shouichi Ohga, Sho Yamasaki, Toshiro Hara
Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (Nod1) in wild-type, SCID, CARD9(-/-) , and MyD88(-/-) mice...
June 22, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28615462/posttranslational-modification-as-a-critical-determinant-of-cytoplasmic-innate-immune-recognition
#6
REVIEW
Paul J Baker, Dominic De Nardo, Fiona Moghaddas, Le Son Tran, Annabell Bachem, Tan Nguyen, Thomas Hayman, Hazel Tye, James E Vince, Sammy Bedoui, Richard L Ferrero, Seth L Masters
Cell surface innate immune receptors can directly detect a variety of extracellular pathogens to which cytoplasmic innate immune sensors are rarely exposed. Instead, within the cytoplasm, the environment is rife with cellular machinery and signaling pathways that are indirectly perturbed by pathogenic microbes to activate intracellular sensors, such as pyrin, NLRP1, NLRP3, or NLRC4. Therefore, subtle changes in key intracellular processes such as phosphorylation, ubiquitination, and other pathways leading to posttranslational protein modification are key determinants of innate immune recognition in the cytoplasm...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28614830/expression-of-tlr2-nod1-and-nod2-and-the-nlrp3-inflammasome-in-renal-tubular-epithelial-cells-of-male-versus-female-mice
#7
Sean E DeWolf, Alana A Shigeoka, Andrew Scheinok, Sashi G Kasimsetty, Alexander K Welch, Dianne B McKay
BACKGROUND: Gender-biased outcomes are associated with acute kidney injury (AKI) and human and animal studies have shown that females are preferentially protected from renal ischemia. However, the reason for this is not known. One clue might lie with pattern recognition receptors (PRRs), which are triggers of ischemic injury when ligated by molecules in the ischemic milieu. Several PRR families are expressed by renal tubular epithelial cells (RTEs) and incite cell death signaling and production of pro-inflammatory molecules...
June 15, 2017: Nephron
https://www.readbyqxmd.com/read/28611823/genetic-variability-as-a-regulator-of-tlr4-and-nod-signaling-in-response-to-bacterial-driven-dna-damage-response-ddr-and-inflammation-focus-on-the-gastrointestinal-gi-tract
#8
REVIEW
Evagelia Spanou, Polyxeni Kalisperati, Ioannis S Pateras, Alexandros Papalampros, Alexandra Barbouti, Athanasios G Tzioufas, Athanassios Kotsinas, Stavros Sougioultzis
The fundamental role of human Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the two most studied pathogen recognition receptors (PRRs), is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28592872/nod1-deficiency-impairs-cd44a-lck-as-well-as-pi3k-akt-pathway
#9
Yi Wei Hu, Xiao Man Wu, Shi Si Ren, Lu Cao, Pin Nie, Ming Xian Chang
Pattern recognition receptors (PRRs) are crucial for host defense and tissue homeostasis against infecting pathogens. PRRs are highly conserved cross species, suggesting their key roles in fundamental biological processes. Though much have been learned for NOD1 receptor in the innate and adaptive immune responses, the roles of NOD1 during embryonic and larval stages remain poorly understood. Here, we report that NOD1 is necessary for the modulation of PI3K-Akt pathway and larval survival in zebrafish. Transcriptome analysis revealed that the significantly enriched pathways in NOD1 (-/-) zebrafish larvae were mainly involved in metabolism and immune system processes...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28578011/homology-modeling-and-in-silico-prediction-of-ulcerative-colitis-associated-polymorphisms-of-nod1
#10
Ishani Majumdar, Isha Nagpal, Jaishree Paul
Cytosolic pattern recognition receptors play key roles in innate immune response. Nucleotide binding and oligomerisation domain containing protein 1 (NOD1) belonging to the Nod-like receptor C (NLRC) sub-family of Nod-like receptors (NLRs) is important for detection and clearance of intra-cellular Gram negative bacteria. NOD1 is involved in activation of pro-inflammatory pathways. Limited structural data is available for NOD1. Using different templates for each domain of NOD1, we determined the full-length homology model of NOD1...
May 31, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28576260/regulation-of-bone-mass-by-the-gut-microbiota-is-dependent-on-nod1-and-nod2-signaling
#11
Claes Ohlsson, Giulia Nigro, Ivo Gomperts Boneca, Fredrik Bäckhed, Philippe Sansonetti, Klara Sjögren
Germ-free (GF) mice have increased bone mass that is normalized by colonization with gut microbiota (GM) from conventionally raised (CONV-R) mice. To determine if innate immune signaling pathways mediated the effect of the GM, we studied the skeleton of GF and CONV-R mice with targeted inactivation of MYD88, NOD1 or NOD2. In contrast to WT and Myd88(-/-) mice, cortical bone thickness in mice lacking Nod1 or Nod2 was not increased under GF conditions. The expression of Tnfα and the osteoclastogenic factor Rankl in bone was reduced in GF compared to CONV-R WT mice but not in Nod1(-/-) or Nod2(-/-) mice indicating that the effect of the GM to increase Tnfα and Rankl in bone and to reduce bone mass is dependent on both NOD1 and NOD2 signaling...
July 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28545134/structures-of-the-inactive-and-active-states-of-rip2-kinase-inform-on-the-mechanism-of-activation
#12
Erika Pellegrini, Luca Signor, Saurabh Singh, Elisabetta Boeri Erba, Stephen Cusack
Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K) is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles...
2017: PloS One
https://www.readbyqxmd.com/read/28541685/discovery-of-1-4-benzodiazepine-2-5-dione-bzd-derivatives-as-dual-nucleotide-binding-oligomerization-domain-containing-1-2-nod1-nod2-antagonists-sensitizing-paclitaxel-ptx-to-suppress-lewis-lung-carcinoma-llc-growth-in-vivo
#13
Suhua Wang, Jingshu Yang, Xueyuan Li, Zijie Liu, Youzhen Wu, Guangxu Si, Yiran Tao, Nan Zhao, Xiao Hu, Yao Ma, Gang Liu
Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Previously, we reported nucleotide-binding oligomerization domain-containing protein 1 (NOD1) antagonists (11, 12) and a NOD2 antagonist (9) that sensitized docetaxel (DTX) or paclitaxel (PTX) treatment for breast or lung cancer. In this article, we describe for the first time a 1,4-benzodiazepine-2,5-dione (BZD) derivative (26bh) that acts as a dual NOD1/NOD2 antagonist and inhibits both nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) inflammatory signaling, thereby sensitizing PTX to suppress Lewis lung carcinoma (LLC) growth...
June 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28539433/slc46-family-transporters-facilitate-cytosolic-innate-immune-recognition-of-monomeric-peptidoglycans
#14
Donggi Paik, Amanda Monahan, Daniel R Caffrey, Roland Elling, William E Goldman, Neal Silverman
Tracheal cytotoxin (TCT), a monomer of DAP-type peptidoglycan from Bordetella pertussis, causes cytopathology in the respiratory epithelia of mammals and robustly triggers the Drosophila Imd pathway. PGRP-LE, a cytosolic innate immune sensor in Drosophila, directly recognizes TCT and triggers the Imd pathway, yet the mechanisms by which TCT accesses the cytosol are poorly understood. In this study, we report that CG8046, a Drosophila SLC46 family transporter, is a novel transporter facilitating cytosolic recognition of TCT, and plays a crucial role in protecting flies against systemic Escherichia coli infection...
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28536249/bronchial-inflammation-and-bacterial-load-in-stable-copd-is-associated-with-tlr4-overexpression
#15
Antonino Di Stefano, Fabio L M Ricciardolo, Gaetano Caramori, Ian M Adcock, Kian Fan Chung, Peter J Barnes, Paola Brun, Andrea Leonardi, Filippo Andò, Davide Vallese, Isabella Gnemmi, Luisella Righi, Francesco Cappello, Bruno Balbi
Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12)...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28534957/grape-seed-proanthocyanidin-inhibits-inflammatory-responses-in-hepatic-stellate-cells-by-modulating-the-mapk-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#16
Jin-Woo Lee, Young Il Kim, Youngchul Kim, Minji Choi, Seoyeon Min, Yong Hoon Joo, Sung-Vin Yim, Namhyun Chung
In the present study, we aimed to investigate the molecular mechanisms and prophylactic effects of grape seed proanthocyanidin (GSP) on lipopolysaccharide (LPS)-stimulated human hepatic stellate cells (HSCs). Cell counting and MTT assays were used to assess cell viability in the absence or presence of GSP. Reverse transcription-quantitative PCR (RT-qPCR) was performed for several inflammation-related genes (NOD1, NOD2, TLR2, TLR4, IL-1 β, IL-6, IL-8, iNOS and COX-2). The expression of anti-inflammatory cell signaling molecules, including c-Jun N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK), Akt, nuclear factor-κB (NF-κB), inhibitory-κBα (IκBα), iNOS and COX-2, was evaluated by western blot analysis...
May 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28514661/innate-recognition-of-intracellular-bacterial-growth-is-driven-by-the-tifa-dependent-cytosolic-surveillance-pathway
#17
Ryan G Gaudet, Cynthia X Guo, Raphael Molinaro, Haila Kottwitz, John R Rohde, Anne-Sophie Dangeard, Cécile Arrieumerlou, Stephen E Girardin, Scott D Gray-Owen
Intestinal epithelial cells (IECs) act as sentinels for incoming pathogens. Cytosol-invasive bacteria, such as Shigella flexneri, trigger a robust pro-inflammatory nuclear factor κB (NF-κB) response from IECs that is believed to depend entirely on the peptidoglycan sensor NOD1. We found that, during Shigella infection, the TRAF-interacting forkhead-associated protein A (TIFA)-dependent cytosolic surveillance pathway, which senses the bacterial metabolite heptose-1,7-bisphosphate (HBP), functions after NOD1 to detect bacteria replicating free in the host cytosol...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28484277/tyrosine-kinase-inhibitors-of-ripk2-attenuate-bacterial-cell-wall-mediated-lipolysis-inflammation-and-dysglycemia
#18
Brittany M Duggan, Kevin P Foley, Brandyn D Henriksbo, Joseph F Cavallari, Akhilesh K Tamrakar, Jonathan D Schertzer
Inflammation underpins aspects of insulin resistance and dysglycemia. Microbiota-derived cell wall components such as muropeptides or endotoxin can trigger changes in host immunity and metabolism. Specific peptidoglycan motifs promote metabolic tissue inflammation, lipolysis and insulin resistance via Nucleotide-binding oligomerization domain-containing protein 1 (Nod1). Receptor-interacting serine/threonine-protein kinase 2 (Ripk2) mediates Nod1-induced immunity, but the role of Ripk2 in metabolism is ill-defined...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28475174/diverse-ubiquitin-linkages-regulate-rip-kinases-mediated-inflammatory-and-cell-death-signaling
#19
REVIEW
Axel Witt, Domagoj Vucic
Members of the RIP kinase family are key regulators of inflammation and cell death signaling implicated in maintaining immune responses and proper tissue homeostasis. Increasing evidence points to post-translational modifications of RIP1, RIP2 and RIP3 as being critical for regulating their function. Ubiquitination and the E3 ligases, such as inhibitors of apoptosis (IAP) proteins and LUBAC, that direct substrate selectivity as well as the deubiquitinating enzymes, such as A20 and OTULIN, that reverse these modifications dictate the outcome of RIP kinase signaling...
May 5, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28434881/muramyl-dipeptide-based-postbiotics-mitigate-obesity-induced-insulin-resistance-via-irf4
#20
Joseph F Cavallari, Morgan D Fullerton, Brittany M Duggan, Kevin P Foley, Emmanuel Denou, Brennan K Smith, Eric M Desjardins, Brandyn D Henriksbo, Kalvin J Kim, Brian R Tuinema, Jennifer C Stearns, David Prescott, Philip Rosenstiel, Brian K Coombes, Gregory R Steinberg, Jonathan D Schertzer
Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. We found that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires NOD2. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss or altering the composition of the microbiome...
May 2, 2017: Cell Metabolism
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