scholarly journals Modification of the Structure of Peptidoglycan Is a Strategy To Avoid Detection by Nucleotide-Binding Oligomerization Domain Protein 1

2006 ◽  
Vol 75 (2) ◽  
pp. 706-713 ◽  
Author(s):  
Margreet A. Wolfert ◽  
Abhijit Roychowdhury ◽  
Geert-Jan Boons

ABSTRACT Nucleotide-binding oligomerization domain (NOD) protein 1 (NOD1) and NOD2 are pathogen recognition receptors that sense breakdown products of peptidoglycan (PGN) (muropeptides). It is shown that a number of these muropeptides can induce tumor necrosis factor alpha (TNF-α) gene expression without significant TNF-α translation. This translation block is lifted when the muropeptides are coincubated with lipopolysaccharide (LPS), thereby accounting for an apparently synergistic effect of the muropeptides with LPS on TNF-α protein production. The compounds that induced synergistic effects were also able to activate NF-κB in a NOD1- or NOD2-dependent manner, implicating these proteins in synergistic TNF-α secretion. It was found that a diaminopimelic acid (DAP)-containing muramyl tetrapeptide could activate NF-κB in a NOD1-dependent manner, demonstrating that an exposed DAP is not essential for NOD1 sensing. The activity was lost when the α-carboxylic acid of iso-glutamic acid was modified as an amide. However, agonists of NOD2, such as muramyl dipeptide and lysine-containing muramyl tripeptides, were not affected by amidation of the α-carboxylic acid of iso-glutamic acid. Many pathogens modify the α-carboxylic acid of iso-glutamic acid of PGN, and thus it appears this is a strategy to avoid recognition by the host innate immune system. This type of immune evasion is in particular relevant for NOD1.

2020 ◽  
Author(s):  
Lida Zare ◽  
Akram Eidi ◽  
Mohammad Safarian ◽  
Mohammad Kazemi Arababadi

Abstract Background Angiography is a safe cardiovascular technique for the diagnosis and treatment of the cardiovascular disorders. The potential effects of angiography on the cytokines are yet to be clarified completely. Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) are the important pro-inflammatory cytokines that participate in the pathogenesis of artery stenosis. The aim of his project was to study the angiography effects on the serum levels of IL-8 and TNF-α. Methods Fifty-five participants in three groups, without, with one and with more than one artery stenosis, were explored in this project. Serum levels of IL-8 and TNF-α were measured in the participants before and after angiography using enzyme linked immunosorbent assay (ELISA) technique. Results Serum levels of IL-8, but not TNF-α, were significantly decreased following angiography. X-ray doses had moderate positive correlation with serum levels of TNF-α in the patients with more than one artery stenosis. Serum levels of IL-8 and TNF-α were not different among male and female participants in all groups. Discussion Angiography may be a protective factor for inflammation in IL-8 dependent manner. Using angiography in the patients with more than one artery stenosis needs to be executed cautiously.


2001 ◽  
Vol 69 (4) ◽  
pp. 2025-2030 ◽  
Author(s):  
Shuhua Yang ◽  
Shunji Sugawara ◽  
Toshihiko Monodane ◽  
Masahiro Nishijima ◽  
Yoshiyuki Adachi ◽  
...  

ABSTRACT Teichuronic acid (TUA), a component of the cell walls of the gram-positive organism Micrococcus luteus (formerlyMicrococcus lysodeikticus), induced inflammatory cytokines in C3H/HeN mice but not in lipopolysaccharide (LPS)-resistant C3H/HeJ mice that have a defect in the Toll-like receptor 4 (TLR4) gene, both in vivo and in vitro, similarly to LPS (T. Monodane, Y. Kawabata, S. Yang, S. Hase, and H. Takada, J. Med. Microbiol. 50:4–12, 2001). In this study, we found that purified TUA (p-TUA) induced tumor necrosis factor alpha (TNF-α) in murine monocytic J774.1 cells but not in mutant LR-9 cells expressing membrane CD14 at a lower level than the parent J774.1 cells. The TNF-α-inducing activity of p-TUA in J774.1 cells was completely inhibited by anti-mouse CD14 monoclonal antibody (MAb). p-TUA also induced interleukin-8 (IL-8) in human monocytic THP-1 cells differentiated to macrophage-like cells expressing CD14. Anti-human CD14 MAb, anti-human TLR4 MAb, and synthetic lipid A precursor IVA, an LPS antagonist, almost completely inhibited the IL-8-inducing ability of p-TUA, as well as LPS, in the differentiated THP-1 cells. Reduced p-TUA did not exhibit any activities in J774.1 or THP-1 cells. These findings strongly suggested that M. luteus TUA activates murine and human monocytic cells in a CD14- and TLR4-dependent manner, similar to LPS.


2004 ◽  
Vol 11 (6) ◽  
pp. 1140-1147 ◽  
Author(s):  
Hidenori Matsuzaki ◽  
Hiroshi Kobayashi ◽  
Tatsuo Yagyu ◽  
Kiyoshi Wakahara ◽  
Toshiharu Kondo ◽  
...  

ABSTRACT Bikunin, a Kunitz-type protease inhibitor, exhibits anti-inflammatory activity in protection against cancer and inflammation. To investigate the molecular mechanism of this inhibition, we analyzed the effect of bikunin on tumor necrosis factor alpha (TNF-α) production in human peripheral mononuclear cells stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Here, we show the following results. (i) LPS induced TNF-α expression in time- and dose-dependent manners through phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathways. (ii) Bikunin inhibits LPS-induced up-regulation of TNF-α protein expression in a dose-dependent manner, reaching 60% inhibition at the highest doses of bikunin tested (5.0 μM). (iii) Inhibition by bikunin of TNF-α induction correlates with the suppressive capacity of ERK1/2, JNK, and p38 signaling pathways, implicating repressions of at least three different signals in the inhibition. (iv) Bikunin blocks the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins. (v) Bikunin is functional in vivo, and this glycoprotein blocks systemic TNF-α release in mice challenged with LPS. (vi) Finally, bikunin can prevent LPS-induced lethality. In conclusion, bikunin significantly inhibits LPS-induced TNF-α production, suggesting a mechanism of anti-inflammation by bikunin through control of cytokine induction during inflammation. Bikunin might be a candidate for the treatment of inflammation, including septic shock.


2005 ◽  
Vol 176 (1) ◽  
pp. 484-490 ◽  
Author(s):  
Bastian Opitz ◽  
Anja Püschel ◽  
Wiebke Beermann ◽  
Andreas C. Hocke ◽  
Stefanie Förster ◽  
...  

2008 ◽  
Vol 134 (4) ◽  
pp. A-16 ◽  
Author(s):  
Tomohiro Watanabe ◽  
Naoki Asano ◽  
Peter Murray ◽  
Keiko Ozato ◽  
Atsushi Kitani ◽  
...  

2010 ◽  
Vol 78 (11) ◽  
pp. 4734-4743 ◽  
Author(s):  
Simone Guglielmetti ◽  
Valentina Taverniti ◽  
Mario Minuzzo ◽  
Stefania Arioli ◽  
Ivan Zanoni ◽  
...  

ABSTRACT The probiotic approach represents an alternative strategy in the prevention and treatment of infectious diseases, not only at the intestinal level but also at other sites of the body where the microbiota plays a role in the maintenance of physiological homeostasis. In this context, we evaluated in vitro the potential abilities of probiotic and dairy bacteria in controlling Streptococcus pyogenes infections at the pharyngeal level. Initially, we analyzed bacterial adhesion to FaDu hypopharyngeal carcinoma cells and the ability to antagonize S. pyogenes on FaDu cell layers and HaCat keratinocytes. Due to its promising adhesive and antagonistic features, we studied the dairy strain Lactobacillus helveticus MIMLh5, also through in vitro immunological experiments. First, we performed quantification of several cytokines and measurement of NF-κB activation in FaDu cells. MIMLh5 efficiently reduced the induction of interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), in a dose-dependent manner. After stimulation of cells with IL-1β, active NF-κB was still markedly lowered. Nevertheless, we observed an increased secretion of IL-6, gamma interferon (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) under these conditions. These effects were associated with the ability of MIMLh5 to enhance the expression of the heat shock protein coding gene hsp70. In addition, MIMLh5 increased the GM-CSF/G-CSF ratio. This is compatible with a switch of the immune response toward a TH1 pathway, as supported by our observation that MIMLh5, once in contact with bone marrow-derived dendritic cells, triggered the secretion of TNF-α and IL-2. In conclusion, we propose MIMLh5 as a potential probiotic bacterium for the human pharynx, with promising antagonistic and immunomodulatory properties.


2012 ◽  
Vol 287 (27) ◽  
pp. 23057-23067 ◽  
Author(s):  
Jinyao Mo ◽  
Joseph P. Boyle ◽  
Christopher B. Howard ◽  
Tom P. Monie ◽  
Beckley K. Davis ◽  
...  

Author(s):  
Sangeeta Mohanty ◽  
Abhisek Pal ◽  
V Badireenath Konkimalla ◽  
Sudam Chandra Si

Objective: The objective of this study was to establish the anti-inflammatory activity of sulforaphane (SFN) in different acute and subchronic models of inflammation. Methods: The anti-inflammatory activity of SFN was evaluated by the secretion of proinflammatory cytokines in rat peripheral blood mononuclear cells (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]) which are important mediators of inflammation as determined by enzyme-linked immunosorbent assay. Furthermore, paw volume was determined in various acute models of inflammation, and percentage inhibition of granuloma tissue was assessed by cotton pellet-induced granuloma model. From serum, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase levels were determined which is followed by assay for estimation of antioxidants such as superoxide dismutase (SOD), catalase, and glutathione (GSH). Results: SFN showed significant anti-inflammatory activity against paw edema induced by carrageenin/histamine/egg-albumin. A remarkable control in inflammation was observed most notably at the highest test dose of 5 mg/kg in the subchronic granuloma model. In addition, the release of inflammatory cytokines such as IL-6 and TNF-α which is responsible for inflammatory activity gets attenuated by SFN (∗p<0.05; ∗∗p< 0.01). Moreover, toxic control rats showed significant decreased levels of GSH, catalase, and SOD and increased the level of serum hepatic enzymes which gets reversed by SFN in dose-dependent manner. Conclusions: The present findings demonstrated that SFN can recover inflammation by inhibiting TNF-α and IL-6 in inflammation process.


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