• Tuberculosis and Respiratory Diseases
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• v.67 no.1
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• pp.14-20
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• 2009

Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-$\alpha$, MIP-2, IL-1$\beta$ and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-$\alpha$ and IL-1$\beta$ was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-$\alpha$ and IL-1$\beta$. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

• The Korean Journal of Food And Nutrition
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• v.36 no.6
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• pp.535-542
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• 2023

We investigated the anti-inflammatory effects of shiitake mushroom and kelp (SMK) mixture extracts in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 cells. Treatment of RAW 264.7 cells with LPS significantly increased NO (nitric oxide) production, pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and IL-1β), and inflammation-related genes (COX-2 and inducible nitric oxide synthase (iNOS)). In cytotoxicity testing using RAW 264.7 cells, SMK mixture extracts in the range of 1-16 ㎍/mL did not inhibit cell proliferation. However, SMK mixture extracts significantly inhibited NO production in a dose-dependent manner (p<0.05). SMK treatment significantly decreased TNF-α, IL-6, IFN-γ, and IL-1β levels compared to the LPS group, and similarly, pro-inflammatory cytokine mRNA levels also decreased. SMK mixture extracts reduced the mRNA expression of COX-2 and iNOS in RAW 264.7 cells compared to LPS (p<0.05). The above results show that SMK mixture extracts suppressed the inflammatory response induced by LPS. In particular, the extracts were shown to regulate the inflammatory response by suppressing the expression of inflammatory cytokines and inflammation-related enzymes.

• The Journal of Internal Korean Medicine
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• v.30 no.3
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• pp.612-623
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• 2009

Objectives : The water extract of Sopung-tang (SPT) has been traditionally used in the treatment of acute stroke in Oriental Medicine. Pro-inflammatory cytokines play a critical role in the onset of post-ischemic inflammatory cascades. The present study was designed to investigate the effects of SPT on pro-inflammatory cytokine production in a photothrombotic ischemia mouse model. Methods : After SPT oral administration to the mice for five days, with using Rose Bengal and cold light, photothrombotic ischemia lesion was induced in stereotactically held male BALB/c mice. Also, results including, gross finding lesion size, histopathological finding changes, and inflammatory cytokine expression changes from the photothrombotic ischemia mouse model were observed. Results : The photothrombotic ischemia lesion was decreased by the oral injection of SPT. Also, SPT inhibited the expression of TNF-$\alpha$, IL-$1{\beta}$, IL-6, the active form of caspase-3 protease, and transglutaminase-2 in the photothrombotic ischemia lesion. Conclusions : These results suggest that SPT protects the ischemic death of brain cells through suppression of the production of anti-inflammatory cytokines and catalytic activation of caspase-3 protease in the photothrombotic ischemia mouse model.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.296-301
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• 2015

Chronic kidney diseases are based on uncontrolled immunological and inflammatory responses to pathophysiological renal circumstances such as glomerulonephritis, which is caused by immunological mechanisms of glomerular inflammation with increased production of renal pro-inflammatory cytokines. Pentoxifylline (PTX) exhibits anti-inflammatory properties by inhibiting cytokine and chemokine production through aggregation of erythrocytes and thrombocytes. We synthesized a series of 1,7-substituted methylxanthine derivatives by the Traube purine reaction, and the formation of purine ring was completed through nitrosation, a reduction of the nitroso to the amine by catalytic hydrogenation as derivatives of PTX. Then we studied biological activities such as renal anti-inflammatory effects of the synthesized compounds in the production of cytokines such as nitric oxide (NO), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) and of chemokines such as monocyte chemoattractant protein-1 and IL-8 in Raw 264.7 and HK-2 cells. Renal antiinflammatory activities of this novel series of N-1 and N-7-substituted methylxanthine showed that the N-7 methyl-group-substituted analogs (S7b) showed selective 61% and 77% inhibition of the production of NO and IL-8. The other replacement of the N-1-(CH₂)₄COCH₃ roup, as in the case of compound S6c, also showed an effective 50% and 77% inhibition of TNF-α and IL-8 production in LPS-stimulated Raw 264.7 and HK-2 cells.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.4
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• pp.36-48
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• 2008

Purpose: The purpose of this study is to investigate anti-inflammatory effect and immune responses of aqueous extract from Fructus Chaenomelis (FC). Methods: We studied anti-inflammatory effect by means of examining the production of NO(nitric oxide) and expressions of pro-inflammatory cytokine (TNF-$\alpha$(tumor necrosis factor-alpha), IL(Interleukin)-6, IL-12) in the LPS-induced peritoneal macrophages of mice. Also, The western blot analysis has been done to look into the mechanism of anti-inflammatory effect. Results: 1. The FC extract did not have any cytotoxicity in the peritoneal macrophages. 2. The FC extract inhibits the productions of NO, IL-6. IL-12 in the LPS-stimulated peritoneal macrophages of mice, but not of TNF-$\alpha$. 3. The FC extract inhibits the activation of NF-${\kappa}B$(nuclear factor-kappa B) by keeping $I{\kappa}B-\alpha$(inhibitory kappa B-alpha) from degradating, but not of MAPKs(mitogen-activated protein kinases) such as ERK(extracelluar signa 1-regulated kinase), JNK(c-Jun N-terminal kinase), p38. Conclusion: These results show that FC extract inhibits the production of pro-inflammatory cytokines such as IL-6. IL-12. NO by inhibiting NF-${\kappa}B$ activation in the peritoneal macrophages of mice. In conclusion, this experiment suggests that FC extract may be effective for the treatment of acute and chronic inflammation including genitourinary infection.

• The Korea Journal of Herbology
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• v.29 no.4
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• pp.69-76
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• 2014

Objectives : Gami-Chunggisan extract (GCE) is one of the oriental traditional medicine. We investigated the antioxidant effect and reduction of pro-inflammatory cytokine as a functional ingredient for cosmetic products from the GCE. Methods : GCE was prepared by extracting with 80% ethanol. We analyzed total polyphenol and antioxidant activities. To evaluate antioxidant activity, we measured 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay. Also we measured the production of reactive oxygen species (ROS) and nitric oxide (NO) on Raw264.7 cells. We researched reduction of anti-inflammatory cytokines from concentration of GCE on Raw264.7 cells. Results : Total polyphenol quantity of GCE was included 46.6 mg/g. The GCE showed ABTS free radical scavenging ability with more than 89% at $1000{\mu}g/m{\ell}$. In addition the DPPH free radical scavenging ability from the GCE was activated over 93% at $1000{\mu}g/m{\ell}$. Production of the ROS was decreased by approximately 26%, upon the GCE treatment at concentration of $100{\mu}g/m{\ell}$. The GCE at $100{\mu}g/m{\ell}$ concentration showed inhibitory effect on NO production by 38%. Production of IL-$1{\beta}$ and IL-6 were decreased by approximately 56% and 36%, respectively upon GCE treatment at $100{\mu}g/m{\ell}$. Also, production of TNF-${\alpha}$ was decreased by approximately 79% at $100{\mu}g/m{\ell}$. Moreover, the GCE showed inhibitory effects on the expression of the IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ genes in LPS-induced Raw 264.7 cells. Conclusions : From the results above, we conclude that the GCE indicated significant antioxidant effects and induced reduction of pro-inflammatory cytokine.

• Parasites, Hosts and Diseases
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• v.55 no.3
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• pp.295-304
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• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• Journal of Life Science
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• v.32 no.5
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• pp.368-374
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• 2022

In this study, the effects of UV irradiation-enhanced ergocalciferol (vitamin D₂) content containing Lentinula edodes extract on inflammation and allergic responses were investigated in vitro. The anti-inflammatory and anti-allergic effects of the mushroom extract were tested by estimating the cytokine secretions, such as TNF-α, IL-6, and IL-1β in LPS-activated macrophages (RAW 264.7), or histamine release in PMA and A23187-activated mast cells (RBL-2H3). Under the condition of macrophage activation with LPS, mushroom extract significantly reduced the secretions of pro-inflammatory cytokines, TNF-α and IL-6, and their mRNA expression also matched the observation. The current mushroom extract also significantly reduced the amount of mast cell degranulation-induced histamine secretion from PMA- and A23187-treated mast cells as well as the reduced secretion of IL-4. These results suggest that mushroom extract, which has increased ergocalciferol content by UV irradiation, inhibits the expression of cytokines in inflammation and allergic reactions; therefore, it can be used effectively for the prevention and treatment of inflammatory and allergic diseases.

• Journal of Embryo Transfer
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• v.31 no.4
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• pp.323-333
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• 2016

Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.490-495
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• 2004

Brain cells produce cytokines and chemokines during the inflammatory process of many neuronal diseases both in animal models and in patients. Inflammatory cytokines are the main responsible for the onset of inflammatory cascade. During the past decade, a growing corpus of evidence has indicated an important role of these cytokines in the development of brain damage. ZhenganXifeng-tang (ZGXFT) is a Korean herbal prescription, which has been successfully applied for the treatment of various neuronal diseases. However, its effect in experimental models remains unknown. Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in inflammatory disease. An inflammatory response associated with β-amyloid (Aβ) and interleukin (IL)-1β is responsible for the pathology of inflammation disease. To investigate the biological effect of ZGXFT, the author examined cytotoxicity, effect of cytokines (IL-6 and IL-8) secretion and expression of cyclooxygenase-2 (COX-2) on human astrocytoma cell line U373MG stimulated with IL-1β plus M fragment 25-35 (Aβ [25-35]). ZGXFT by itself had no effect on cell viability on human astrocytoma cells. The secretion of IL-6 and IL-8 was inhibited by pre-treatment with ZGXFT in human astrocytoma cells. In addition, the expression of COX-2 was induced by IL-1β plus AB[25-35] and was partially inhibited by treatment with ZGXFT. The author demonstrates the regulatory effects of inflammatory reactions by ZGXFT in human astrocytes for the first time and suggest the anti-inflammatory effect of ZGXFT may reduce and delay pathologic events of inflammatory disease.