• Journal of Life Science
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• v.21 no.1
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• pp.36-43
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• 2011

Diabetes mellitus is associated with vascular complications. Diabetic patients exhibit high levels of glycated adducts in serum compared to non-diabetic individuals. The aim of this study was to investigate whether extracellular glycated albumin (GA) predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells (AoSMCs) to GA not only enhanced interleukin-6 (IL-6) release but also activated promoter activity of the IL-6 gene. GA-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-2 and TIR-domain-containing adapter-inducing interferon-$\beta$ (TRIF). Extracellular signal-regulated kinase (ERK) inhibition and diphenyleneiodium (DPI) also attenuated IL-6 induction by GA. Mutation at the nuclear factor-${\kappa}B$ (NF-${\kappa}B$)-binding site in the IL-6 promoter region suppressed promoter activation in response to GA. The present study proposes that GA would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4, EKR, and NF-${\kappa}B$ play active roles in the process.

• Journal of Microbiology and Biotechnology
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• v.19 no.6
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• pp.616-621
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• 2009

To evaluate the effects of lactic acid bacteria (LAB) in inflammatory bowel diseases (IBD), we measured the inhibitory effect of several LAB isolated from intestinal microflora and commercial probiotics against the glycosaminoglycan (GAG) degradation by intestinal bacteria. Bifidobacterium longum HY8004 and Lactobacillus plantarum AK8-4 exhibited the most potent inhibition. These LAB inhibited colon shortening and myeloperoxidase production in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitic mice. These LAB also blocked the expression of the proinflammatory cytokines, IL-$1{\beta}$ and TNF-$\alpha$, as well as of COX-2, in the colon. LAB also blocked activation of the transcription factor, NF-${\kappa}B$, and expression of TLR-4 induced by TNBS. In addition, LAB reduced the TNBS-induced bacterial degradation activities of chondroitin sulfate and hyaluronic acid. These findings suggest that GAG degradation-inhibitory LAB may improve colitis by inhibiting inflammatory cytokine expression via TLR-4-linked NF-${\kappa}B$ activation and by inhibiting intestinal bacterial GAG degradation.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.827-843
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• 2023

BACKGROUND/OBJECTIVES: Mitochondrial DNA leakage leads to inflammatory responses via endosome activation. This study aims to evaluate whether the perennial grass water extract (Pogonatherum panicum) ameliorate mitochondrial DNA (mtDNA) leakage. MATERIALS/METHODS: The major bioactive constituents of P. paniceum (PPW) were investigated by high-performance liquid chromatography, after which their antioxidant activities were assessed. In addition, RAW 264.7 macrophages were stimulated with lipopolysaccharide, resulting in mitochondrial damage. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to examine the gene expression and cytokines. RESULTS: Our results showed that PPW extract-treated activated cells significantly decrease reactive oxygen species and nitric oxide levels by reducing the p2^phox and iNOS expression and lowering cytokine-encoding genes, including IL-6, TNF-α, IL-1β, PG-E2 and IFN-γ relative to the lipopolysaccharide (LPS)-activated macrophages. Furthermore, we observed that LPS enhanced the mtDNA leaked into the cytoplasm, increasing the transcription of Tlr9 and signaling both MyD88/Irf7-dependent interferon and MyD88/NF-κb p65-dependent inflammatory cytokine mRNA expression but which was alleviated in the presence of PPW extract. CONCLUSIONS: Our data show that PPW extract has antioxidant and anti-inflammatory activities by facilitating mtDNA leakage and lowering the Tlr9 expression and signaling activation.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.184-184
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• 2002

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.184-184
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• 2002

In our previous study, we reported that PG, a polysaccharide isolated from Plyatycodon grandiflorum, activated macrophages and B cells, but not T cells. Here, we investigated in more detail the mechanism of action of PG in macrophage activation.(omitted)

• Journal of fish pathology
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• v.34 no.2
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• pp.185-199
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• 2021

Vibriosis is an important septicemic bacterial disease that affects a variety of commercial fish species, including cultured Dicentrarchus labrax. Nanotechnology has become an important modern tool for fish diseases prevention. Furthermore, nanomaterials have the ability to prevent and treat fish diseases. The current study was aimed to identify the causative agent of massive mortality of D. labrax commercial farm in Alexandria, Egypt. Experimental infection and the median lethal dose (LD50) of pathogenic isolate were assessed. Also, the effect of ginger nanoparticles (GNPs) and Sacchromyces cerevisiae as feed additives for prevention of vibriosis in D. labrax was carried out. Similarly, the tissue immunstimulant genes, IL-1β and TLR2 were measured in the spleen of feeding groups. The clinical signs of naturally diseased D. labrax showed corneal opacity and paleness of gills with excessive mucous secretion. The post-mortem abnormalities were severe hemorrhage and adhesion of internal organs. After bacteriological isolation and identification, the causative agent of mortality in the current study was Vibrio alginolyticus. The LD₅₀ of V. alginolyticus was 1.5×10^5.4 CFU/ml. The experimentally infected D. labrax showed ulceration, exophthalmia and skin hemorrhages. The post-mortem findings of the experimentally infected D. labrax revealed internal hemorrhage, spleen darkness and paleness of liver. There is no mortality and 100% RPS in groups fed GNPs then injected with V. alginolyticus, in those fed a combination of GNPs and S. cerevisiae and a group fed normal diet then injected with physiological saline (control negative), respectively. Contrarily, there was 10% mortality and 87.5 RPS in the group fed S. cerevisae then injected with V. alginolyticus. On the other hand, the control positive group showed 79% mortality. The spleen IL-1β and TLR2 immunostimulant genes were significantly increased in groups of fish fed GNNP, S. cerevisiae and a combination of GNPs and S. cerevisiae, respectively compared to control group. The highest stimulation of those immunostimulant genes was found in the group fed a combination of GNPs and S. cerevisiae, while fish fed S. cerevisiae had the lowest level. Dietary combination of GNPs and S. cerevisiae was shown to be efficient in preventing of vibriosis, with greatest stimulation of spleen IL-1β and TLR2 immunostimulant genes.

• Journal of Life Science
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• v.31 no.4
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• pp.389-399
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• 2021

This study determined the effects of Centella asiatica leaf on H₂O₂ induced cell cycle arrest, mitochondrial activity, and proinflammatory cytokine production in human dermal fibroblast (HDF) cells. We used an 80% methanol extract of C. asiatica, its ethyl acetate fraction, and asiaticoside, the major constituent of C. asiatica. The C. asiatica extract, its ethyl acetate fraction, and asiaticoside attenuated G1 cell cycle-arrest and the apoptotic effect caused by H₂O₂-induced oxidative stress. The cells treated with C. asiatica extract, its ethyl acetate fraction, and asiaticoside secreted lower levels of TNF-α and IL-6. The antioxidant effect of asiaticoside was higher than that of C. asiatica extract and its ethyl acetate fraction. Treatment with C. asiatica extract, its ethyl acetate fraction, and asiaticoside also increased the mitochondrial membrane potential and restored normal mitochondrial morphology. Following H₂O₂ stress induction, cells treated with C. asiatica extract, its ethyl acetate fraction, and asiaticoside showed increased mitochondrial oxygen consumption rates and decreases in the TLR4-MyD88-TRAF6-p65 pathway activity. These findings suggest that C. asiatica extract, its ethyl acetate fraction, and asiaticoside have antioxidant and anti-inflammatory effects, as well as the ability to control the mitochondrial activities of HDF cells.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.187-192
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.

• Food Science of Animal Resources
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• v.42 no.1
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• pp.84-97
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• 2022

We evaluated the anti-biofilm formation and anti-inflammatory activity of Hovenia monofloral honey (HMH) against Enterococcus faecalis. Co-culture of HMH with E. faecalis attenuated the biofilm formation of E. faecalis on a polystyrene surface. In addition, HMH effectively eradicated the established E. faecalis biofilm. HMH significantly attenuated E. faecalis growth but did not affect the production of extracellular polymeric substances on E. faecalis, indicating that reduction of E. faecalis biofilm is a result of HMH-mediated killing of E. faecalis. Furthermore, we found that HMH can effectively attenuate E. faecalis-induced expression of a proinflammatory interleukin-8 (IL- 8) in HT-29 cells. Interestingly, treatment of HMH significantly attenuated the E. faecalis-mediated expression of Toll-like receptor-2 (TLR-2) and its adaptor molecules, myeloid differentiation primary response 88 (MyD88), in HT-29 cells. In addition, E. faecalis-induced mitogen-activated protein kinases (MAPKs) phosphorylation was significantly attenuated by HMH administration. Furthermore, HMH-mediated antiinflammatory efficacy (0.2 mg/mL of HMHs) had an equal extent of inhibitory efficacy as 5 μM of MyD88 inhibitor to attenuate E. faecalis-mediated IL-8 expression in HT-29 cells. These results suggest that HMH could effectively inhibit E. faecalis-mediated gastrointestinal inflammation through regulating the TLR-2/MyD88/MAPKs signaling pathways. Collectively, our data suggest that HMH could be developed as a potential natural agent to control E. faecalis-mediated biofilm formation and inflammation.

• Journal of Applied Biological Chemistry
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• v.54 no.4
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• pp.279-283
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• 2011

Toll-like receptors (TLRs) play an important role in induction of innate immune responses. The activation of TLRs triggers inflammatory responses that are essential for host defense against invading pathogens. Phenethyl isothiocyanate (PEITC) extracted from cruciferous vegetables has an effect on anti-inflammatory therapy. Dysregulated activation of nuclear factor-${\kappa}$B (NF-${\kappa}$B), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) has been shown to play important roles in the development of certain inflammatory disease. To evaluate the therapeutic potential of PEITC, NF-${\kappa}$B activation and COX-2 and iNOS expression induced by lipopolysaccharide (LPS, TLR4 agonist), polyinosinic-polycytidylic acid (Poly[I:C], TLR3 agonist), 2 kDa macrophageactivating lipopeptide (MALP-2, TLR2 and TLR6 agonist) or oligodeoxynucleotide 1668 (ODN1668, TLR9 agonist) were examined. PEITC inhibits the activation of NF-${\kappa}$B induced by LPS or Poly[I:C] but not by MALP-2 or ODN1668. PEITC also suppressed the iNOS expression induced by LPS or Poly[I:C]. However, PEITC did not suppress COX-2 expression induced by LPS, Poly[I:C], MALP-2, or ODN1668. These results suggest that PEITC has the specific mechanism for antiinflammatory responses.