• 대한한의학방제학회지
• /
• 제16권2호
• /
• pp.219-228
• /
• 2008

Objective : The present study was designed to investigate whether the water extract of the root of Scutellaria baicalensis could regulate lipopolysaccharide (LPS)-induced type 1 interferon. Methods : To evaluate of type 1 interferon inhibitory effect of the root of Scutellaria baicalensis, we examined type 1 interferon in LPS-stimulated RAW264.7 cells. Furthermore, Interleukin (IL)-10 and interferon regulatory factor (IRF) - 1, 7 expression level were examined to study the inhibition mechanisms. Results 1. Extract from the root of Scutellaria baicalensis didn't have any cytotoxity itelf. 2. Extract from the root of Scutellaria baicalensis inhibited interferon-a,b in dose dependant- and type 1 interferon production in time dependant manner. 3. Extract from the root of Scutellaria baicalensis reduced IL-10 and IRF-1, 7 production in LPS-stimulated RAW 264.7 cells. Conclusion : The extract from the root of Scutellaria baicalensis down-regulated LPS-induced type 1 interferon through suppression of IL-10 and IRF-1, 7 expression. This results suggested that the extract from the root of Scutellaria baicalensis may be a beneficial drug against inflammatory diseases.

• Clinical and Experimental Pediatrics
• /
• 제51권9호
• /
• pp.1007-1011
• /
• 2008

목 적 : 열성 경련은 소아에서 가장 흔한 경련의 원인으로 우리나라의 경우 6-9%의 발생율을 보인다. 열성 경련의 원인으로 유전적인 소인이 중요한 것으로 생각되고 있지만 아직까지 열성경련과 관련된 정확한 유전자는 밝혀지지 않았다. $IL-1{\beta}$은 내인성 발열인자로서 열성 경련의 발병에 중요한 역할을 할 것으로 생각된다. 방 법 : 40명의 열성경련 환아(가족형 20명, 산발형 20명)와 33명의 대조군을 대상으로 하여 말초혈액에서 DNA를 추출했으며 PCR을 통해 분석하였다. $IL-1{\beta}$ gene의 -31, -511 promoter region에서 C/T biallelic polymorphism의 빈도를 대조군과 단순 열성경련 군(가족형과 산발형)으로 나누어 각각 비교해 보았다. 결 과 : 두 군간 다형성의 빈도는 통계학적으로 유의한 차이를 보이지 않았다. 결 론 : 통계학적 의의는 없으나 가족력이 있는 열성경련 군에서 CT/CT의 빈도가 상대적으로 높게(70.0%) 측정되어 많은 수의 환아를 대상으로 한 연구가 필요할 것으로 보인다.

• 대한한방내과학회지
• /
• 제28권2호
• /
• pp.262-274
• /
• 2007

Objective : It has been reported that two-repeats ($IL1RN^{\ast}2$) of interleukin-1 receptor antagonist (IL-1Ra) gene is associated with ischemic stroke, and that Ala allele of the common Pro12Ala polymorphism in $PPAR-{\gamma}2$ isoform is associated with reduced risk for type 2 DM and its complications. The aim of the present study is to assess the association of IL-1Ra and $PPAR-{\gamma}2$ Pro12Ala polymorphism with the presence of ischemic stroke in the case of diabetic and non-diabetic patients. Methods : Genomic DNA was obtained from 373 healthy subjects, 157 DM subjects without ischemic stroke (known DM duration ${\ge}10$ years) and 302 ischemic stroke patients (including with DM). IL-1Ra polymorphism was analysed by polymerase chain reaction (PCR), and $PPAR-{\gamma}2$ polymorphism by restriction fragment length polymorphism after PCR. Results : $IL1RN^{\ast}1/IL1RN^{\ast}2$ genotype was associated with significantly increased risk for DM (OR=2.86, P = 0.0008) and ischemic stroke (OR=2.74, P = 0.0016). Pro/Ala genotype was associated with the reduced risk for DM (OR=0.53, P = 0.0491) and ischemic stroke (OR=0.38, P = 0.0039). They were also associated with the reduced risk for ischemic stroke in the DM patients compared with DM without ischemic stroke (OR=0.25, P = 0.0321). Conclusions : $IL1RN^{\ast}2$ allele could be an accelerating factor, not a predictive marker for ischemic stroke in type 2 DM. The Pro/Ala genotype of $PPAR-{\gamma}2$ Pro12Ala polymorphism may be associated with reduced risk for ischemic stroke with type 2 DM. Therefore it could be a useful predictive marker for ischemic stroke in Korean type 2 DM.

• 생명과학회지
• /
• 제26권9호
• /
• pp.1082-1087
• /
• 2016

본 연구에서는 염증성 사이토카인 IL-1α가 소장의 tight junction (TJ)의 integrity에 미치는 영향을 평가하고 항염증 효능이 있다고 알려진 curcumin (CCM)이 IL-1α에 의한 TJ 손상 예방효과를 알아보고자 Caco-2 세포 모델을 이용하여 실험하였다. Caco-2 세포 단층의 TJ integrity에 대한 IL-1α의 영향을 FITC-dextran flux와 transepithelial electrical resistance (TEER)를 측정하여 검증하였다. IL-1α를 100 ng/ml의 농도로 Caco-2 세포 단층의 상부에 24시간 동안 처리하였을 때 처리 2시간 이후 FITC-dextran의 flux가 유의적으로 증가하였고, IL-1α 처리시간에 비례하여 상승하였다. 또한 IL-1α의 처리는 TEER 값을 유의적으로 감소시켜 IL-1α에 의한 TJ 손상을 확인할 수 있었다. 반면 CCM의 전처리는 이러한 IL-1α에 의한 TJ 기능 저하를 거의 완전히 예방하는 것을 알 수 있었다. 이상의 결과로 염증성 사이토카인 IL-1α이 TJ의 integrity 조절에 부정적인 영향을 미치며 이는 강황에서 발견되는 CCM 전처리에 의해 효과적으로 억제될 수 있음을 보여준다. 본 연구 결과와 관련되어 TJ 구성단백질 발현 및 작용 기작에 대한 분자세포생물학적 연구와 in vivo 연구가 필요하다.

• Nutrition Research and Practice
• /
• 제14권5호
• /
• pp.453-462
• /
• 2020

BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG), an oriental herbal medicine, has been known to improve liver function, and has both anti-inflammatory and antimicrobial properties. However, little is known about the immune-enhancing effects of PG and its mechanism. In this study, we aimed to investigate whether fermented PG extract (FPGE), which has increased platycodin D content, activates the immune response in a murine macrophage cell line, RAW 264.7. MATERIALS/METHODS: Cell viability was determined by Cell Counting Kit-8 assay and the nitric oxide (NO) levels were measured using Griess reagent. Cytokine messenger RNA levels of were monitored by quantitative reverse transcription polymerase chain reaction. To investigate the molecular mechanisms underlying immunomodulatory actions of FPGE in RAW 264.7 cells, we have conducted luciferase reporter gene assay and western blotting. RESULTS: We found that FPGE treatment induced macrophage cell proliferation in a dose-dependent manner. FPGE also modulated the expression of NO and pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The activation and phosphorylation levels of nuclear factor kappa B (NF-κB) were increased by FPGE treatment. Moreover, 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of AMP-activated kinase (AMPK), significantly reduced both lipopolysaccharides- and FPGE-induced NF-κB reporter gene activity. CONCLUSIONS: Taken together, our findings suggest that FPGE may be a novel immune-enhancing agent acting via AMPK-NF-κB signaling pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권5호
• /
• pp.471-479
• /
• 2023

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

• Biomolecules & Therapeutics
• /
• 제31권2호
• /
• pp.210-218
• /
• 2023

Prostate cancer is the fifth leading cause of cancer-related mortality in men, primarily because of treatment resistance, recurrence, and metastasis. In the present study, we investigated the role of paracrine interleukin-8 (IL-8) in the antagonistic expression of IL-8 and androgen receptor (AR), and the contribution of IL-8 to prostate cancer aggressiveness. In hormone-responsive LNCaP cells that do not express IL-8, recombinant IL-8 treatment significantly increased expressions of IL-8, CXC chemokine receptor 2 (CXCR2), matrix metalloproteinase (MMP)-2/9, Snail, and vimentin. IL-8 treatment significantly decreased AR and E-cadherin expression. IL-8-induced gene expression changes were suppressed by navarixin, a CXCR1/2 inhibitor, and gallein, a Gβγ inhibitor. In PC-3 androgen-refractory prostate cancer cells, IL-8 knockdown reduced expressions of CXCR2, MMP-2/9, Snail, and vimentin, and increased AR and E-cadherin expressions at the mRNA and protein levels. Co-culture with MEG-01 human megakaryocytic cells secreting high levels of IL-8 induced gene expression changes in both LNCaP and PC-3 cells, similar to those induced by IL-8 treatment. The altered gene expressions were accompanied by significant activation of transcription factor Snail in LNCaP and PC-3 cells. Treatment with the CXCR blocker navarixin inhibited the invasion of PC-3 cells but not LNCaP cells. However, invasion induced by MEG-01 was inhibited by navarixin in both LNCaP and PC-3 cells. The collective findings demonstrate that IL-8 enhances CXCR2 expression, which antagonistically regulates AR expression. More importantly, through changes in IL-8/CXCR2-regulated gene expression, IL-8 induces antiandrogen therapy resistance and epithelial-mesenchymal transition in prostate cancer.

• 대한한방부인과학회지
• /
• 제22권3호
• /
• pp.83-98
• /
• 2009

Purpose: This study was performed to evaluate the anti-inflammatory effect of Eungapbang extract (EGB). Methods: To evaluate the anti-inflammatory effects of EGB, we nourished RAW 264.7 cell lines in the laboratory dish. Next, inflammatory cytokine concentrations were analyzed. Then, sera were prepared from blood after lipopolysaccharide (LPS) injection in chemically induced mouse models of intestinal inflammation, and Interleukin-1${\beta}$ (IL-1${\beta}$), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-${\alpha}$) were measured using ELISA kits. Results: 1. EGB significantly suppressed the expression levels of IL-1${\beta}$ and NOS-II genes at 100, 50 and 10 ${\mu}g/m{\ell}$ concentrations, and IL-6, TNF-${\alpha}$ and COX-2 mRNAs at 100 and 50 ${\mu}g/m{\ell}$ concentrations. 2. EGB significantly reduced the production level of IL-1${\beta}$ and TNF-${\alpha}$ at 100${\mu}g/m{\ell}$ concentrations, and IL-6 at 100 and 50 ${\mu}g/m{\ell}$ concentrations. 3. EGB significantly decreased the production level of IL-1${\beta}$ and IL-6 in sera of acute inflammation induced mice. 4. EGB could suppress the expression level of IL-1${\beta}$ and IL-6 mRNA in spleen tissues in acute inflammation induced mice. Conclusion: On the basis of the above results, it is confirmed that the anti-inflammatory effects of EGB were recognized. Therefore, EGB is recommended as promising therapy for treatment of such ailments as pelvic inflammatory disease.

• Journal of Microbiology and Biotechnology
• /
• 제17권2호
• /
• pp.348-358
• /
• 2007

Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. $Na\ddot{i}ve\;CD4^+$ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, $TGF-{\gamma}$, and repressor of GATA, but more $IFN-{\gamma}$ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove $na\ddot{i}ve$ wild-type $CD4^+\;T$ cells to differentiate into cells producing more IL-10 and $TGF-{\beta}$, but less $IFN-{\gamma}$ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10-and $TGF-{\beta}$-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

• Journal of Microbiology and Biotechnology
• /
• 제29권1호
• /
• pp.151-159
• /
• 2019

Lipoteichoic acid isolated from Lactobacillus plantarum K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of $TNF-{\alpha}$ and interleukin (IL)-6. In addition, pLTA increases the survival rate of mice in a septic shock model. In the current study, we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail, pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However, $TNF-{\alpha}$ production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and $TNF-{\alpha}$ induced by PGE-2 and LPS in PMA-differentiated THP-1 cells were mediated by pLTA, but not by other LTAs isolated from either Staphylococcus aureus (aLTA) or L. sakei (sLTA). Further studies revealed that pLTA-mediated IL-10 inhibition and $TNF-{\alpha}$ induction in PGE-2+LPS-stimulated PMA-differentiated THP-1 cells were mediated by dephosphorylation of p38 and phosphorylation of c-Jun N-terminal kinase (JNK), respectively. Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231), which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells. Taken together, our data suggest that pLTA contributes to inflammatory homeostasis through induction of repressed pro-inflammatory cytokines as well as inhibition of excessive anti-inflammatory cytokines.