• Title/Summary/Keyword: pro-inflammatory elements

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Pro-(IL-18) and Anti-(IL-10) Inflammatory Promoter Genetic Variants (Intrinsic Factors) with Tobacco Exposure (Extrinsic Factors) May Influence Susceptibility and Severity of Prostate Carcinoma: A Prospective Study

  • Dwivedi, Shailendra;Singh, Sarvesh;Goel, Apul;Khattri, Sanjay;Mandhani, Anil;Sharma, Praveen;Misra, Sanjeev;Pant, Kamlesh Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3173-3181
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    • 2015
  • Background: It has been hypothesized that IL-18 (pro-) and IL-10 (anti-) inflammatory genetic variants at -607 C/A-137G/C and -819C/T,-592C/A, respectively, may generate susceptibility and severity risk with various modes of tobacco exposure in prostate carcinoma (PCa) patients. IL-18 is a pro-inflammatory cytokine expressed on various cells including prostate gland elements, and is a key mediator of immune responses with anti-cancerous properties. IL-10 is an anti-inflammatory cytokine that is associated with tumour malignancy which causes immune escape. Materials and Methods: The present study was conducted with 540 subjects, comprising 269 prostate carcinoma patients and 271 controls. Genotyping was performed by PCR-RFLP and confirmed by real time PCR probe-based methods. Results: The findings indicated that the mutant heterozygous and homozygous genotype CC and GC+CC showed significant negative associations (p=0.01, OR=0.21; 95% CI: 0.08-0.51 and p=0.011, OR=0.43; 95% CI: 0.22-0.81, respectively) thus, less chance to be diagnosed as cancer against GG genotype of tobacco smoking patients. In addition, a heterozygous GC genotype at the same locus of IL-18 pro-inflammatory cytokine may aggravate the severity (OR=2.82; 95%CI 1.09-7.29 :p=001) so that patients are more likely to be diagnosed in advanced stage than with the GG wild homozygous genotype. Our results also illustrated that anti-inflammatory cytokine (IL-10) genetic variants, although showing no significant association with susceptibility to cancer of the prostate, may gave profound effects on severity of the disease, as -819 TC (OR=4.60; 95%CI 1.35-15.73), and -592 AC (OR=5.04; 95%CI 1.08-25.43) of IL-10 in tobacco chewers and combined users (both chewers and smokers) respectively, are associated with diagnosis in more advanced stage than with other variants. Conclusions: We conclude that promoter genetic variants of IL-18 and IL-10 with various modes of tobacco exposure may affect not only susceptibility risk but also severity in prostate cancer.

The effect of prescriptions prepared by adding medicinal herbs(Rehmannia glutinosa Residue, Poria cocos Bark) and fermenting herbal materials based on formulas Iksuyoungjingo on immunological activity (익수영진고가미방의 지황박, 복령피 배합과 발효에 따른 제제가 면역활성에 미치는 영향)

  • Lee, Yu-Mi;Kim, Wang-In;Choi, Dong-Hee;Kim, Mi-Rae;Moon, Yang-Seon;Kim, Ji-Eun;Youn, Dae-Hwan;Son, Hong-Seok;Na, Chang-Su
    • Herbal Formula Science
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    • v.26 no.1
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    • pp.13-26
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    • 2018
  • Objectives : This study was carried out to enhance the activity of Iksuyoungjingo, which has the tonify Qi, nourish Yin effect of oriental medicine, and to study the effect of the prescriptions on the immunological activities. Methods : Immunosuppression was induced by methotrexate (MTX) 2 mg / kg, the experimental group was divided into IYGgami-I, IYGgami-I-F, IYGgami-II and IYGgami-II-F groups. Each prescription was administered with drinking water for 20 days, and body weight was measured every 5 days during this period. Leukocyte, $TNF-{\alpha}$, IL-2, IL-6, IgE, spleen weight and body weight were measured Results : In the changes of $TNF-{\alpha}$, IL-2 and IL-6 as pro-inflammatory elements, all of the experimental groups showed a significant increase compared to the control group. In the IgE changes, the IYGgami-I-F, IYGgami-II and IYGgami-II-F groups showed a significant decrease compared to the control group. In the changes of spleen weight, the IYGgami-II-F group showed a significant increase compared to the control group. In the changes of WBC and lymphocytes, the IYGgami-I-F group showed a significant increase compared to the control group. Conclusions : From the above results, it can be observed that the efficacy against immunity is exerted in all of the preparations, and it was confirmed that the efficacy was maintained constant even when utilizing the Rehmannia glutinosa Residue and Poria cocos Bark, and that a more beneficial effect can be exerted in the effectiveness when the fermentation is carried out.

Anti-inflammatory Efficacy of HK Shiitake Mushroom Mycelium in LPS-treated RAW 264.7 Cells Through Down-regulation of NF-κB Activation (LPS로 활성화한 RAW 264.7 세포에서 HK표고버섯균사체의 NF-κB 활성 억제를 통한 항염증 효과)

  • Song, Chae Yeong;Oh, Tae Woo;Kim, Hoon Hwan;Lee, Yu Bin;Kim, Jeong Ok;Kim, Gon Sup;Ha, Yeong Lae
    • Journal of Life Science
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    • v.32 no.7
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    • pp.491-500
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    • 2022
  • HK shiitake mushroom mycelium (HKSMM), containing 14% β-glucan, is a health functional food ingredient individually approved by the Korea Ministry of Food and Drug Safety for liver health. The anti-inflammatory effect of a 50% aqueous ethanol extract of HKSMM (designated HKSMM50) was studied in RAW 264.7 macrophage cells treated with lipopolysaccharide (LPS). An active hexose correlated compound (AHCC) was used as a positive control. LPS-activated RAW 264.7 cells were treated with HKSMM50 and AHCC (0, 20, 100, 500 ㎍/ml) and cultured for 24 hr. Inflammation-related elements in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA) kits, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in the cells was analyzed by Western blotting. The HKSMM50 lowered iNOS and COX-2 protein expressions, and nuclear factor-kappa B (NF-κB), nitric oxide (NO) and prostaglandin E2 (PGE2) contents in a concentration-dependent manner as compared to LPS treatment. Similarly, the HKSMM50 lowered the content of pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-6 (IL-6) contents and increased the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The efficacy of the AHCC treatment was similar to that of the HKSSM50 treatments. These results indicate that HKSMM50 showed an anti-inflammatory effect in LPS-treated RAW 264.7 cells by down-regulation of NF-κB signaling and suggest that HKSMM could be used as a health functional food ingredient to help improve immune function.

Caffeic Acid Phenethyl Ester Induces the Expression of NAG-1 via Activating Transcription Factor 3 (ATF3를 통한 caffeic acid phenethyl ester에 의한 NAG-1 유전자의 발현 증가)

  • Park, Min-Hee;Chung, Chungwook;Lee, Seong Ho;Baek, Seung Joon;Kim, Jong Sik
    • Journal of Life Science
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    • v.28 no.1
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    • pp.37-42
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    • 2018
  • Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor beta (TGF-${\beta}$) superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. In the present study, we investigated if caffeic acid phenethyl ester (CAPE) derived from propolis could induce the expression of anti-tumorigenic gene NAG-1. Our results indicate that CAPE significantly induced NAG-1 expression in a time- and concentration-dependent manner in HCT116 cells. We also found that CAPE induced NAG-1 expression in a concentration-dependent manner in another human colorectal cancer cell line, LOVO. In addition, CAPE triggered apoptosis, which was detected with Western blot analysis using poly-(ADP-ribose) polymerase antibody. NAG-1 induction by CAPE was not dependent on transcription factor p53, which was confirmed with Western blot analysis using p53 null HCT116 cells. The luciferase assay results indicated that the new cis-elements candidates were located between -474 and -1,086 of the NAG-1 gene promoter. CAPE dramatically induced activating transcription factor 3 (ATF3) expression, but not cAMP response element-binding protein (CREB), which shares the same binding sites with ATF3. The co-transfection experiment with pCG-ATF3 and pCREB showed that only ATF3 was associated with NAG-1 up-regulation by CAPE, whereas CREB had no effect. In conclusion, the results suggest that CAPE could induce the expression of anti-tumorigenic gene NAG-1 mainly through ATF3.

Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes

  • Yeo, Hyunjin;Lee, Jeong Yeon;Kim, JuHwan;Ahn, Sung Shin;Jeong, Jeong You;Choi, Ji Hye;Lee, Young Han;Shin, Soon Young
    • BMB Reports
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    • v.53 no.6
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    • pp.323-328
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    • 2020
  • Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.