• The Journal of Korean Medicine
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• v.26 no.4
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• pp.1-11
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• 2005

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from Cerebral infarction(CI) patients. Methods: We examined how the inhibition rate of tumor necrosis factor (TNF)-$\alpha$, interleukin(IL)-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or desferrioxamine(DFX)treated cells compared to unstimulated cells. Results: DCWGG inhibited the productions of TNF-$\alpha$, IL-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 induced by LPS in a dose-dependent manner. Conclusions: DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.929-935
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• 2006

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral mononuclear cells (PBMCS) from Cerebral infarction(CI) patients. Methods: We examined that the inhibition rate of tumor necrosis factor $(TNF)-{\alpha},\;interleukin(IL)-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or Oesferrioxamine(DFX)-treated cells compared to unstimulated cells. DCWGG inhibited the productions of $TNF-{\alpha},\;IL-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 induced by LPS in a dose-dependent manner DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.1
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• pp.79-83
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• 2004

In order to investigate the beneficial effects of parsely (Petroselinurn sativum) extract on skin, we measured the synthesis of total collagen and type I procollagen in cultured normal human fibroblast (NHF), the synthesis of prostaglandin E$_2$(PCE$_2$), interleukin 1 ${\alpha}$(IL -1 ${\alpha}$) and tumor necrosis factor ${\alpha}$ (TNF ${\alpha}$) in HaCaT cell and we also measured dermal thickness and density in hairless mouse (Female albino hairless mice, Skh:hr-1). As the results, the synthesis of total collagen and type I procollagen were increased 23％ and 18％ respectively, after 1 $\mu\textrm{g}$/mL parsley extract treatment. The producions of PGE$_2$ induced by UVB irradiation were decreased 60％ after 1 $\mu\textrm{g}$/mL parsley extract treatment. The treatment with 1 $\mu\textrm{g}$/mL parsley extract also decreased the synthesis of IL -1 ${\alpha}$ and TNF ${\alpha}$ induced by 10 uM RA, 100 $\mu\textrm{g}$/mL SLS and 30 mJ/$\textrm{cm}^2$ UVB irradiation, After 4 days treatment with 1％ parsley extract, the dermal thickness of hairless mouse was increased 1.5 times and the density of dermis was tighter than control. These results indicate that parsley extract have anti-aging and anti-irritation effects on skin.

• Biomedical Science Letters
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• v.18 no.3
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• pp.181-192
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• 2012

Toll-like receptors (TLRs) induce innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways; myeloid differential factor 88 (MyD88) and Toll/IL-1R domain-containing adaptor inducing IFN-${\beta}$ (TRIF) leading to the activation of NF-${\kappa}B$ and IRF3. Numerous studies demonstrated that certain phytochemicals possessing anti-inflammatory effects inhibit NF-${\kappa}B$ activation induced by pro-inflammatory stimuli including lipopolysaccharide and tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$). However, the direct molecular targets for such anti-inflammatory phytochemicals are not fully identified. In this paper, we will discuss about the molecular targets of phytochemicals in TLRs signaling pathways. These results present a novel anti-inflammatory mechanism of phytochemicals in TLRs signaling.

• BMB Reports
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• v.50 no.11
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• pp.584-589
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• 2017

Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-${\alpha}$, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-${\alpha}$. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ${\kappa}B$ ($I{\kappa}B$)-kinase ${\beta}$ ($IKK{\beta}$) at Ser177/181. This dephosphorylation led to the stabilization of $I{\kappa}B{\alpha}$ and inhibition of NF-${\kappa}B$ activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-$IKK{\beta}$ and inhibiting NF-${\kappa}B$ signaling.

• Molecules and Cells
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• v.46 no.7
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• pp.430-440
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• 2023

Linear ubiquitin chain assembly complex (LUBAC) is a ubiquitin E3 ligase complex composed of HOIP, HOIL-1L, and SHARPIN that catalyzes the formation of linear/M1-linked ubiquitin chain. It has been shown to play a pivotal role in the nuclear factor (NF)-κB signaling induced by proinflammatory stimuli. Here, we found that tumor susceptibility gene (TSG101) physically interacts with HOIP, a catalytic component of LUBAC, and potentiates LUBAC activity. Depletion of TSG101 expression by RNA interference decreased TNFα-induced linear ubiquitination and the formation of TNFα receptor 1 signaling complex (TNF-RSC). Furthermore, TSG101 facilitated the TNFα-induced stimulation of the NF-κB pathway. Thus, we suggest that TSG101 functions as a positive modulator of HOIP that mediates TNFα-induced NF-κB signaling pathway.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.113-119
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• 2013

Objectives : The purpose of this study was to investigate the effects of Angelicae Gigantis Radix Water Extract(AG) on the production of proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide(LPS). Method : RAW 264.7 cells were cotreated with AG(50 and 100 ug/mL) and lipopolysaccharide(LPS; 1 ug/mL) for 24 hours. After 24 hour treatment, using Bead-based multiplex cytokine assay, concentrations of various cytokines such as interleukin(IL)-6, IL-$1{\beta}$, IL-10, tumor necrosis factor-alpha(TNF-${\alpha}$), granulocyte colony-stimulating factor(G-CSF), granulocyte macrophage colony-stimulating factor(GM-CSF), interferon inducible protein-10(IP-10), leukemia inhibitory factor(LIF), lipopolysaccharide-induced chemokine(LIX), monocyte chemoattractant protein-1(MCP-1), macrophage colony-stimulating factor(M-CSF), macrophage inflammatory protein(MIP)-$1{\alpha}$, MIP-$1{\beta}$, MIP-2, Regulated on Activation, Normal T cell Expressed and Secreted(RANTES) and vascular endothelial growth factor(VEGF) were measured. Result : AG significantly inhibited LPS-induced production of TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, and M-CSF from LPS-stimulated RAW 264.7 cells at the concentrations of 50 and 100 ug/mL. AG significantly inhibited LPS-induced production of MIP-$1{\beta}$, MIP-2, GM-CSF, and IL-6 from LPS-stimulated RAW 264.7 cells at the concentrations of 50 ug/mL. AG significantly inhibited LPS-induced production of VEGF from LPS-stimulated RAW 264.7 cells at the concentrations of 100 ug/mL. But AG did not show any significant effect on the production of MCP-1, LIF, LIX, IP-10 and IL-$1{\beta}$ from LPS-induced RAW 264.7 cells. Conclusion : These results suggest that AG has anti-inflammatory effect related with its inhibition of proinflammatory mediators such as TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, MIP-$1{\beta}$, MIP-2, GM-CSF, IL-6, VEGF and M-CSF in LPS-induced macrophages.

• The Korean Journal of Pain
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• v.36 no.1
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• pp.72-83
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• 2023

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

• Journal of Life Science
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• v.23 no.9
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• pp.1140-1146
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• 2013

The effect of dried mackerel extract on the production of nitric oxide (NO) and cytokines, including interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was investigated. All extracts and fractions from dried mackerel significantly reduced NO production induced by lipopolysaccharide (LPS). Among the extracts, acetone+methylene chloride (A+M), n-hexane, and 85% aqueous methanol (MeOH) showed the strongest inhibitory effects. The 85% aqueous MeOH fraction at a concentration of $10{\mu}g$ significantly decreased LPS-induced IL-6 and TNF-${\alpha}$ production after 6 hr of incubation. In the case of LPS-induced IFN-${\gamma}$ production, the 85% aqueous MeOH fraction decreased the production of IFN-${\gamma}$ afer 6, 24, and 72 hr of incubation in a dose-dependent manner. The results show that an 85% aqueous MeOH fraction inhibits the production of NO and proinflammatory cytokines (IL-6, TNF-${\alpha}$, IFN-${\gamma}$), suggesting that this fraction acts as a potent immunomodulator.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7243-7249
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• 2013

Numerous studies have been conducted regarding association between TNF-${\alpha}$ and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-${\alpha}$-308G>A and four also concerned the TNF-${\alpha}$-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-${\alpha}$-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-${\alpha}$-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-${\alpha}$ polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-${\alpha}$-308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-${\alpha}$-238G>A may cause an increase.