Methylglyoxal induced activation of murine peritoneal macrophages and surface markers of T lymphocytes in Sarcoma-180 bearing mice: Involvement of MAP kinase, NF-κβ signal transduction pathway

Pal, Aparajita; Bhattacharya, Iman; Bhattacharya, Sayantani Sarkar; Mandal, Chitra; Ray, Manju

doi:10.1016/j.molimm.2009.03.014

Cited by 27 publications

(23 citation statements)

References 17 publications

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“…32,33 On the IL-10 and peritoneal fibrosis A Onishi et al other hand, several kinds of MGO-mediated processes have been shown to be implicated in the accelerated productions of TNF-α, IL-1β, and IL-6 in macrophages. 34,35 In addition, the overexpression of TNF-α or IL-1β in the peritoneum has been shown to be able to induce an increased expression of TGF-β along with fibronectin expression and collagen deposition as well as an acute inflammatory response. 36 IL-10 was originally described as cytokine synthesis inhibitory factor.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Ōnishi

Akimoto

Urabe

et al. 2015

Laboratory Investigation

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Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we examined the benefits of interleukin (IL)-10, which exerts anti-inflammatory effects, in an experimental rat model of methylglyoxal (MGO)-induced PF. We injected an adeno-associated virus (AAV) vector encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male Sprague-Dawley rats at 6 weeks of age. Four weeks later, the rats received continuous peritoneal injections of conventional PD fluid (PDF) with MGO for 3 weeks. Then, the peritoneal histology and the expression levels of fibrogenic mediators and proinflammatory cytokines were analyzed. The rats demonstrating persistent IL-10 expression showed significantly reduced fibrous peritoneal thickening compared with those with GFP expression. The infiltration of macrophages, the expression of tumor necrosis factor-α, IL-1β, IL-6, transforming growth factor-β1, Snail, and matrix metalloproteinase 2 genes as well as the proliferation of mesenchymallike mesothelial cells augmented by MGO were all significantly suppressed by IL-10 expression. IL-10 also abrogated the extent of MGO-induced bowel adhesions mimicking a cocoon-like mass. Our findings provide valuable insight into the potential benefit of immunomodulation with IL-10 as one potentially effective therapeutic strategy for preventing the onset of peritoneal injury resulting in PF.

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Section: Discussionmentioning

confidence: 99%

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Ōnishi

Akimoto

Urabe

et al. 2015

Laboratory Investigation

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“…The influence of MG on the MAPK pathway has recently also been reported by others [38,39]. Fan et al used MG modified bovine serum albumin to identify the mechanism of TNF-a secretion.…”

Section: Discussionmentioning

confidence: 61%

“…This activation leads to a site-specific phosphorylation of the inhibitor protein IkB by IkB kinases (IKK), consecutive rapid dissociation of the heteromer and subsequently transmigration into the nucleus. Here, they can induce gene transcription by binding to specific promoter elements in the IL-8 gene [39,42]. Furthermore, enhanced transcription levels of NF-kB could also be responsible for the induced IL-8 expression and secretion.…”

Section: Discussionmentioning

confidence: 99%

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Carbonyl compounds methylglyoxal and glyoxal affect interleukin‐8 secretion in intestinal cells by superoxide anion generation and activation of MAPK p38

Kuntz

Kunz

Rudloff

2010

Molecular Nutrition Food Res

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The carbonyl compounds methylglyoxal (MG) and glyoxal (GL) are reactive intermediates of glucose degradation pathways and capable of inducing cellular damage. Although immune-stimulating activity has been investigated in endothelial cells, little is known about the signaling pathways of cytokine induction of these compounds in the intestine. Hence, we investigated the impact of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) on IL-8 production by human intestinal cells (Caco-2 and HT-29) after stimulation by MG and GL. Both compounds induced a dose-dependent enhancement of IL-8 secretion in human intestinal cells. MAPK p38 and extracellular signal-regulated kinase (ERK) were phosphorylated in these cells after having been stimulated by MG and GL. Furthermore, inhibitors of MAPK p38 (SB 203580 and 239063), ERK1/2 (PD 98059) and NF-κB activation (SM-7368 and SC-514) reduced IL-8 secretion. The most important mechanism by which MG and GL induced IL-8 secretion was the generation of superoxide anions which was confirmed by the inhibition of the cytosolic NADPH oxidase with diphenyl iodonium (DPI) or by application of superoxide dismutase (SOD). Our data suggest that multiple pathways were simultaneously activated; however, superoxide dependent MAPK p38 activation seems to be the most dominant pathway for IL-8 secretion in intestinal cells.

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“…9 MG can also activate macrophages 10 via superoxide and nitrite production through the MAPK/NF-κB signaling pathway. 11 These findings paved the way for anticancer drug development using MG as a key component. 12,13 A major problem with using MG as an anticancer drug is that MG, being a normal metabolite, is rapidly degraded by various enzymes present in the body.…”

Section: Introductionmentioning

confidence: 98%

Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

Pal

Talukdar

Roy

et al. 2015

IJN

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Purpose The normal metabolite methylglyoxal (MG) specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon normal cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest in developing a nanoparticulate drug delivery system to protect it and also to enhance its efficacy. Materials and methods MG-conjugated chitosan nanoparticles (Nano-MG) were prepared by conjugating the carbonyl group of MG with the amino group of chitosan polymer (Schiff’s base formation). Nano-MG were characterized in detail using the dynamic light scattering method, zeta potential measurement, Fourier transform infrared spectroscopy, and transmission electron microscopic analysis. Amount of MG anchored to Nano-MG, stability of Nano-MG, and in vitro release of MG from Nano-MG were estimated spectrophotometrically. Ehrlich ascites carcinoma (EAC) cells, human breast cancer cell line HBL-100, and lung epithelial adenocarcinoma cell line A549 were used as test systems to compare Nano-MG with bare MG in vitro. Cytotoxicity to EAC cells was evaluated by the trypan blue dye exclusion test, and cell viability of HBL-100 and A549 cells were studied using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of HBL-100 cells was assessed by flow cytometry and confocal microscopy. In vivo studies were performed on both EAC cells inoculated and also in sarcoma-180-induced solid tumor-bearing Swiss albino mice to assess the anticancer activity of Nano-MG in comparison to bare MG with varying doses, times, and administrative routes. Results Fourier transform infrared spectroscopy revealed the presence of imine groups in Nano-MG due to conjugation of the amino group of chitosan and carbonyl group of MG with diameters of nanoparticles ranging from 50–100 nm. The zeta potential of Nano-MG was +21 mV and they contained approximately 100 μg of MG in 1 mL of solution. In vitro studies with Nano-MG showed higher cytotoxicity and enhanced rate of apoptosis in the HBL-100 cell line in comparison with bare MG, but no detrimental effect on normal mouse myoblast cell line C2C12 at the concerned doses. Studies with EAC cells also showed increased cell death of nearly 1.5 times. Nano-MG had similar cytotoxic effects on A549 cells. In vivo studies further demonstrated the efficacy of Nano-MG over bare MG and found them to be about 400 times more potent in EAC-bearing mice and nearly 80 times more effective in sarcoma-180-bearing mice. Administration of ascorbic acid and creatine during in vivo treatments augmented the anticancer effect of Nano-MG. Conclusion The results clearly indicate that Nano-MG may constitute a promising tool in anticancer therapeutics in the near future.

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Methylglyoxal induced activation of murine peritoneal macrophages and surface markers of T lymphocytes in Sarcoma-180 bearing mice: Involvement of MAP kinase, NF-κβ signal transduction pathway

Cited by 27 publications

References 17 publications

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Carbonyl compounds methylglyoxal and glyoxal affect interleukin‐8 secretion in intestinal cells by superoxide anion generation and activation of MAPK p38

Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

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Methylglyoxal induced activation of murine peritoneal macrophages and surface markers of T lymphocytes in Sarcoma-180 bearing mice: Involvement of MAP kinase, NF-κβ signal transduction pathway

Cited by 27 publications

References 17 publications

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Carbonyl compounds methylglyoxal and glyoxal affect interleukin‐8 secretion in intestinal cells by superoxide anion generation and activation of MAPK p38

Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of&nbsp;its anticancer effect

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Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect