scholarly journals Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain

2005 ◽  
Vol 170 (3) ◽  
pp. 477-485 ◽  
Author(s):  
Lynda M. Stuart ◽  
Jiusheng Deng ◽  
Jessica M. Silver ◽  
Kazue Takahashi ◽  
Anita A. Tseng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mutational Analysis ◽  
Scavenger Receptor ◽  
Lipoteichoic Acid ◽  
Cytoplasmic Domain ◽  
Toll Like Receptor ◽  
Factor Α ◽  
First Time ◽  
Necrosis Factor

Phagocyte recognition and clearance of bacteria play essential roles in the host response to infection. In an on-going forward genetic screen, we identify the Drosophila melanogaster scavenger receptor Croquemort as a receptor for Staphylococcus aureus, implicating for the first time the CD36 family as phagocytic receptors for bacteria. In transfection assays, the mammalian Croquemort paralogue CD36 confers binding and internalization of Gram-positive and, to a lesser extent, Gram-negative bacteria. By mutational analysis, we show that internalization of S. aureus and its component lipoteichoic acid requires the COOH-terminal cytoplasmic portion of CD36, specifically Y463 and C464, which activates Toll-like receptor (TLR) 2/6 signaling. Macrophages lacking CD36 demonstrate reduced internalization of S. aureus and its component lipoteichoic acid, accompanied by a marked defect in tumor necrosis factor-α and IL-12 production. As a result, Cd36−/− mice fail to efficiently clear S. aureus in vivo resulting in profound bacteraemia. Thus, response to S. aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain, which initiates TLR2/6 signaling.

scholarly journals Staphylococcus aureus Peptidoglycan Is a Toll-Like Receptor 2 Activator: a Reevaluation

2005 ◽  
Vol 73 (8) ◽  
pp. 5212-5216 ◽  
Author(s):  
Roman Dziarski ◽  
Dipika Gupta
Keyword(s):  
Staphylococcus Aureus ◽  
Sodium Dodecyl ◽  
Lipoteichoic Acid ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Phenol Extraction ◽  
Tlr2 Activation ◽  
Toll Like Receptor 2 ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Since the ability of peptidoglycan (PGN) to activate Toll-like receptor 2 (TLR2) was recently questioned, we reevaluated activation of TLR2 by PGN. Polymeric soluble or insoluble Staphylococcus aureus PGN, repurified by sodium dodecyl sulfate or phenol extraction, activated TLR2 at 0.1 to 1 or 10 μg/ml, respectively, and induced tumor necrosis factor alpha production. The TLR2 activation by PGN, but not by lipoteichoic acid, was abolished by muramidase digestion. We conclude that polymeric S. aureus PGN is a TLR2 activator.

scholarly journals Divergent roles of Toll-like receptor 2 in response to lipoteichoic acid and Staphylococcus aureus in vivo

2010 ◽  
Vol 40 (6) ◽  
pp. 1639-1650 ◽  
Author(s):  
Mark R. Gillrie ◽  
Lori Zbytnuik ◽  
Erin McAvoy ◽  
Roxna Kapadia ◽  
Kristine Lee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Lipoteichoic Acid ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
And Staphylococcus Aureus

scholarly journals Erlotinib protects against LPS-induced Endotoxicity because TLR4 needs EGFR to signal

2015 ◽  
Vol 112 (31) ◽  
pp. 9680-9685 ◽  
Author(s):  
Sarmishtha De ◽  
Hao Zhou ◽  
David DeSantis ◽  
Colleen M. Croniger ◽  
Xiaoxia Li ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Egf Receptor ◽  
Egfr Inhibitor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Egfr Expression ◽  
Factor Α ◽  
Necrosis Factor

Several components of the canonical pathway of response to lipopolysaccharide (LPS) are required for the EGF-dependent activation of NFκB. Conversely, the ability of Toll-like Receptor 4 (TLR4) to activate NFκB in response to LPS is impaired by down regulating EGF receptor (EGFR) expression or by using the EGFR inhibitor erlotinib. The LYN proto-oncogene (LYN) is required for signaling in both directions. LYN binds to the EGFR upon LPS stimulation, and erlotinib impairs this association. In mice, erlotinib blocks the LPS-induced expression of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) and ameliorates LPS-induced endotoxity, revealing that EGFR is essential for LPS-induced signaling in vivo.

Synthesis of 8-alkoxy-1,3-dimethyl-2, 6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides as analgesic and anti-inflammatory agents

2015 ◽  
Vol 21 (5) ◽  
pp. 273-278 ◽  
Author(s):  
Grażyna Chłoń-Rzepa ◽  
Agnieszka W. Jankowska ◽  
Małgorzata Zygmunt ◽  
Krzysztof Pociecha ◽  
Elżbieta Wyska
Keyword(s):  
Analgesic Activity ◽  
Structural Element ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Peripheral Mechanism ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Inhibit Tumor Necrosis Factor

AbstractA series of new 8-alkoxy-1,3-dimethyl-2,6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides 6–12 was synthesized and evaluated for the analgesic activity in two in vivo models: the writhing syndrome and the hot-plate tests. Among the investigated derivatives, compounds with N′-arylidenehydrazide moiety 9–12 show analgesic activity significantly higher than that of acetylsalicylic acid, which may indicate the importance of this structural element for analgesic properties. The lack of the activity in the hot-plate test may suggest that the analgesic activity of the newly synthesized compounds is mediated by a peripheral mechanism. The selected compounds 7 and 12 inhibit tumor necrosis factor α production in a rat model of lipopolysaccharide-induced endotoxemia, similarly to theophylline, which may confirm their anti-inflammatory properties.

scholarly journals In Vivo and in Vitro Evidence for the Involvement of Tumor Necrosis Factor-α in the Induction of Leptin by Lipopolysaccharide*

Endocrinology ◽  
1998 ◽  
Vol 139 (5) ◽  
pp. 2278-2283 ◽  
Author(s):  
Brian N. Finck ◽  
Keith W. Kelley ◽  
Robert Dantzer ◽  
Rodney W. Johnson
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity

2001 ◽  
Vol 195 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Mauritius Menges ◽  
Susanne Rößner ◽  
Constanze Voigtländer ◽  
Heike Schindler ◽  
Nicole A. Kukutsch ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Immunity ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-α (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10–producing CD4+ T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-α results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10–producing T cells in vivo and prevent EAE.

Nonstressed rat model of acute endotoxemia that unmasks the endotoxin-induced TNF-α response

1999 ◽  
Vol 276 (2) ◽  
pp. H671-H678 ◽  
Author(s):  
David W. A. Beno ◽  
Robert E. Kimura
Keyword(s):  
Rat Model ◽  
Endotoxic Shock ◽  
Stress Hormones ◽  
Tnf Α ◽  
Baseline Concentrations ◽  
Experimental Protocols ◽  
Factor Α ◽  
Necrosis Factor

Previous investigators have demonstrated that the tumor necrosis factor-α (TNF-α) response to endotoxin is inhibited by exogenous corticosterone or catecholamines both in vitro and in vivo, whereas others have reported that surgical and nonsurgical stress increase the endogenous concentrations of these stress-induced hormones. We hypothesized that elevated endogenous stress hormones resultant from experimental protocols attenuated the endotoxin-induced TNF-α response. We used a chronically catheterized rat model to demonstrate that the endotoxin-induced TNF-α response is 10- to 50-fold greater in nonstressed (NS) rats compared with either surgical-stressed (SS, laparotomy) or nonsurgical-stressed (NSS, tail vein injection) models. Compared with the NS group, the SS and NSS groups demonstrated significantly lower mean peak TNF-α responses at 2 mg/kg and 6 μg/kg endotoxin [NS 111.8 ± 6.5 ng/ml and 64.3 ± 5.9 ng/ml, respectively, vs. SS 3.9 ± 1.1 ng/ml ( P < 0.01) and 1.3 ± 0.5 ng/ml ( P < 0.01) or NSS 5.2 ± 3.2 ng/ml ( P < 0.01) at 6 μg/kg]. Similarly, baseline concentrations of corticosterone and catecholamines were significantly lower in the NSS group [84.5 ± 16.5 ng/ml and 199.8 ± 26.2 pg/ml, respectively, vs. SS group 257.2 ± 35.7 ng/ml ( P< 0.01) and 467.5 ± 52.2 pg/ml ( P < 0.01) or NS group 168.6 ± 14.4 ng/ml ( P < 0.01) and 1,109.9 ± 140.7 pg/ml ( P < 0.01)]. These findings suggest that the surgical and nonsurgical stress inherent in experimental protocols increases baseline stress hormones, masking the endotoxin-induced TNF-α response. Subsequent studies of endotoxic shock should control for the effects of protocol-induced stress and should measure and report baseline concentrations of corticosterone and catecholamines.

scholarly journals Evaluation In Vivo and In Vitro of the Antioxidant, Antinociceptive, and Anti-Inflammatory Activities of Biflavonoids From Ouratea hexasperma and O. ferruginea

2019 ◽  
Vol 14 (6) ◽  
pp. 1934578X1985680 ◽  
Author(s):  
Poliana de Araujo Oliveira ◽  
Queli Cristina Fidelis ◽  
Thayane Ferreira da Costa Fernandes ◽  
Milene Conceição de Souza ◽  
Dayane Magalhães Coutinho ◽  
...  
Keyword(s):  
Type I Collagen ◽  
In Vivo Model ◽  
Type I ◽  
Anti Inflammatory ◽  
Vitro Model ◽  
Factor Α ◽  
Necrosis Factor

Ouratea species are used for the treatment of inflammation-related diseases such as rheumatism and arthritic disorders. The Ouratea genus is a rich source of flavonoids and bioflavonoids and for this reason we evaluated the effects of the biflavonoid fractions from the leaves of O. hexasperma (OHME) and O. ferruginea (OFME) in the in vivo model of complete Freund’s adjuvant (CFA)-induced arthritis and in the in vitro model of oxidative stress and cellular viability. The CFA-induced arthritis model in rats was followed by paw volume, articular incapacitation and Randall-selitto models, as well as quantification of cytokines and serum C-terminal telopeptide of type I collagen levels. OHME and OFME demonstrated antinociceptive and anti-inflammatory activities, as well as improvement in articular incapacity and reduction in levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α, and type 1 collagen, and increased cell viability. No adverse effects were observed. The results suggest that OHME and OFME can reduce inflammation and bone resorption besides their antioxidant action.

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