• Journal of Microbiology and Biotechnology
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• v.20 no.11
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• pp.1585-1591
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• 2010

A comprehensive study on the production of inflammatory mediators in the lungs of BALB/c mice following infection with Stenotrophomonas maltophilia was conducted. The levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-${\alpha}$), and interleukin-1${\beta}$ (IL-1${\beta}$) were raised in the lungs of infected mice compared with control. The production of anti-inflammatory cytokine IL-10 was slightly delayed. Its peak level was on the $2^{nd}$ day, whereas the peak of pro-inflammatory cytokines was observed on day 1 after intranasal challenge. This was accompanied by a rise in myeloperoxidase (MPO) and malondialdehyde (MDA) on day 1. The increase in MPO levels matched with histopathological observations, as neutrophils infiltration was detected on the first day. Alveolar macrophages (AMs) obtained from infected animals showed a higher rate of uptake and killing when exposed to bacteria in vitro, compared with similar experiments conducted with AMs from normal mice (control). This suggests that AMs were more efficient in cleaning the bacteria. The nitric oxide (NO) production however started early during infection but reached its maximum on the $3^{rd}$ day. No mortality was observed among the infected animals, and infection was resolved by the $5^{th}$ day post infection. No drastic changes in the lung tissue were observed on histopathological examination.

• Journal of Applied Biological Chemistry
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• v.63 no.2
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• pp.117-123
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• 2020

We examined the anti-inflammatory effect of the peel extract of the newly bred Korean apple (Malus domestica Borkh.) cultivar Green ball. To test its possible use as anti-inflammatory functional material, Raw 264.7 macrophages were treated with pro-inflammatory lipopolysaccharide (LPS) in the presence or absence of Green ball apple peel ethanol extract (GBE). Notably, up to 500 ㎍/mL of GBE did not result in any signs of inhibition on cellular metabolic activity or cytotoxicity in Raw 264.7 macrophages. Supplementation with GBE to LPS-treated Raw 264.7 macrophage significantly suppressed various pro-inflammatory responses in a dose-dependent manner, including i) nitric oxide (NO) production, ii) accumulation of inducible NO synthase and cyclooxygenase-2, iii) phosphorylation of nuclear factor-kappa B (NF-κB) subunit p65, and iv) expression of pro-inflammatory biomarker genes, including tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2.

• BMB Reports
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• v.45 no.9
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• pp.526-531
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• 2012

Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-${\alpha}$)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. TNF-${\alpha}$-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-${\alpha}$-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-${\alpha}$-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.6.1-6.20
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• 2020

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• Biomedical Science Letters
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• v.21 no.4
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• pp.218-226
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• 2015

The present study investigated the mechanisms of licochalcone B (LicB)-mediated inhibition of the inflammatory response in murine macrophages. RAW264.7 murine macrophages were cultured in the absence or presence of lipopolysacharide (LPS) with LicB. LicB suppressed the generation of nitric oxide and the pro-inflammatory cytokines interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor-${\alpha}$. LicB also inhibited the expression of mRNA for inducible nitric oxide synthase and pro-inflammatory cytokines induced by LPS. Moreover, LicB inhibited nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 translocation into the nucleus in a dose-dependent manner. Thus, LicB mainly exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-${\kappa}B$ and activator protein-1 signaling pathways in macrophages, which subsequently diminishes the expression and release of various inflammatory mediators. LicB shows promise as a therapeutic agent in inflammatory diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4609-4615
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• 2014

Background: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). Materials and Methods: Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-$1{\alpha}$, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied. Results: Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-$1{\alpha}$ was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01). Conclusions: ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-$1{\alpha}$ and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3939-3944
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• 2014

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.3
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• pp.176-182
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• 2016

When inflammatory reaction is in progress, the macrophages release inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and product inflammatory mediators, including inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2). We conducted this study to evaluate the anti-inflammatory efficacy on each water extract of Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex, and to investigate whether they inhibit the expression of pro-inflammatory cytokine. Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex were extracted with water and freeze-dried. Acanthoside D, 20-hydroxyecdysone, and pinoresinol diglucoside as an index material were analyzed by high-performance liquid chromatography (HPLC) to ensure that the components of each extracts were extracted well. RAW 264.7 cell line, stimulated with lipopolysaccharide (LPS) to cause an inflammatory response, was treated with each water extract at various concentrations to determine the anti-inflammatory efficacy. Then, the anti-inflammatory efficacy was confirmed by a nitric oxide (NO) assay, and the mRNA expression levels of pro-inflammatory cytokines were measured by real time PCR. As a result, the indicator materials were detected from each extract, and Acanthopanacis cortex water extract (ACWE) and Achyranthes radix water extract (ARWE) were shown to have a high activity than Eucommiae cortex water extract (ECWE) in NO assay. In Korea, traditionally it prescribed a combination of medicinal herbs. This study confirmed the anti-inflammatory response of these medicinal plants in arthritis and its synergistic effect when used in combination with western medicine.

• Journal of Korean Medicine for Obesity Research
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• v.16 no.2
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• pp.85-91
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• 2016

Objectives: This study investigated the effects of Scutellariae Radix extract (SRE) on lipids metabolism, oxidation and the production of pro-inflammatory cytokines in rats fed highly oxidized fat. Methods: To induce obesity, male Sprague‐Dawley rats were fed a highly oxidized fat diet for 10 weeks. SRE at 100 mg/kg were administered orally to obesity-induced rats for 6 weeks, and their lipid metabolism, oxidation and production of pro-inflammatory cytokines were examined. Results: The concentrations of free fatty acid, triglyceride, total cholesterol, and low density lipoprotein-cholesterol in plasma decreased in SRE-treated groups, although the difference was not significant between control and SRE-treated groups, while that of high density lipoprotein-cholesterol significantly increased in SRE group. The concentrations of total cholesterol and triglyceride in the liver were tended to decrease in SRE-treated group. The concentrations of thiobarbituric acid in plasma and liver were lower in SRE group than in control group. The levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in plasma were decreased in SRE group. Activities of glutathione peroxidase, superoxide dismutase, and catalase in liver were tended to increase in the SRE group. The plasma concentrations of interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$ and IL-6 were lower in SRE group than in control group, while that of IL-10 was higher. The liver concentrations of $IL-1{\beta}$, $TNF-{\alpha}$, and IL-6 were tended to decrease while that of IL-10 tended to increase in SRE group. Conclusions: Finally SRE could be used in the production of nutraceuticals for lowering lipids and exerting anti-oxidation and anti-inflammatory effects in obesity rats fed highly oxidized rat.

• BMB Reports
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• v.48 no.2
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• pp.81-90
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• 2015

p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation. The importance of p73-induced apoptosis lies in its capability to substitute the pro-apoptotic activity of p53 in various human cancer cells in which p53 is mutated or inactive. Despite the great importance of p73-induced apoptosis in cancer therapy, little is known about the molecular basis of p73-induced apoptosis. In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.