• 치위생과학회지
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• 제17권1호
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• pp.81-86
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• 2017

Bacterial infection and smoking are an important risk factors involved in the development and progression of periodontitis. However, the signaling mechanism underlying the host immune response is not fully understood in periodontal lesions. In this study, we determined the expression of janus kinase (JAK)/signal transducer and activator of transcription (STAT) on Porphyromonas gingivalis lipopolysaccharide (LPS)- and nicotine-induced cytotoxicity and the production of inflammatory mediators, using osteoblasts. The cells were cultured with 5 mM nicotine in the presence of $1{\mu}g/ml$ LPS. Cell viability was determined using MTT assay. The role of JAK on inflammatory mediator expression and production, and the regulatory mechanisms involved were assessed via enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blot analysis. LPS- and nicotine synergistically induced the production of cyclooxgenase-2 (COX-2) and prostaglandin $E_2$ ($PGE_2$) and increased the protein expression of JAK/STAT. Treatment with an JAK inhibitor blocked the production of COX-2 and $PGE_2$ as well as the expression of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$ ($IL-1{\beta}$), and IL-6 in LPS- and nicotine-stimulated osteoblasts. These results suggest that JAK/STAT is closely related to the LPS- and nicotine-induced inflammatory effects and is likely to regulate the immune response in periodontal disease associated with dental plaque and smoking.

• ALGAE
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• 제29권4호
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• pp.333-341
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• 2014

In this study, four compounds isolated from the red alga Laurencia snackeyi were evaluated for their potential anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These compounds were tested for their inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. Since $5{\beta}$-hydroxypalisadin B showed the best activity it was further tested for the production of prostaglandin-$E_2$ ($PGE_2$), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the release of pro-inflammatory cytokines tumor necrotic factor-alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). $5{\beta}$-Hydroxypalisadin B significantly reduced the $PGE_2$ release and suppressed the iNOS and COX-2 expression in LPS-stimulated RAW 264.7 cells. It also significantly reduced the release of pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These findings provide the first evidence of anti-inflammatory potential of $5{\beta}$-hydroxypalisadin B isolated from the red alga L. snackeyi and hence, it could be exploited as an active ingredient in pharmaceutical, nutraceutical and functional food applications.

• Tuberculosis and Respiratory Diseases
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• 제67권4호
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• pp.303-310
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• 2009

Background: Elevated expression of cyclooxygenase-2 (COX-2) and Polo-like kinase-1 (PLK-1) is observed in a wide variety of cancers. Augmented expression of COX-2 and enhanced production of prostaglandin $E_2(PGE_2)$ are associated with increased tumor cell survival and malignancy; COX-2 has been implicated in the control of human non-small cell lung carcinoma (NSCLC) cell growth. PLK-1 siRNA induced the cell death of lung cancer cells and the systemic administration of PLK-1 siRNA/atelocollagen complex inhibited the growth of lung cancer in a liver metastatic murine model. COX-2 and PLK-1 are involved in proliferation and in cell cycle regulation, and there is a significant correlation between their interaction in prostate carcinoma. Methods: In this study, we investigated the pattern of COX-2 and PLK-1 expression in NSCLC, after treatment with IL-1$\beta$, COX-2 inhibitor and PLK-1 siRNA. Results: Expression of PLK-1 was decreased in A549 COX-2 sense cells, and was increased in A549 COX-2 anti-sense cells. Knock out of PLK-1 expression by PLK-1 siRNA augmented COX-2 expression in A549 and NCl-H157 cells. When A549 and NCI-H157 cells were treated with COX-2 inhibitor on a dose-dependent basis, PLK-1 and COX-2 were reduced. However, when the expression of COX-2 was induced by IL-1$\beta$, the production of PLK-1 decreased. Conclusion: These results demonstrate that COX-2 and PLK-1 are regulated and inhibited by each other in NSCLC, and suggest that these proteins have a reverse relationship in NSCLC.

• 한국약용작물학회지
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• 제17권5호
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• pp.321-327
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• 2009

Sunlight, and in particular its UV component, is the major environmental trigger that underlies the major signs of human skin and skin cancer in general. Therefore, this study was carried out to investigate the UV protection effects of R. coreanus. R. coreanus was extracted by ultra high pressure extraction process at 500 MPa and $30^{\circ}C$ for 5 and 15 minutes. The cytotoxicity of the extracts extracted by ultra high pressure process on human dermal fibroblast cell CCD-986sk, human kidney normal cell HEK293, and human lung normal cell HEL299 was measured as 17.5%, 16.5% and 14.0%, respectively in adding $1.0\;mg/m{\ell}$ of the samples, which was much lower than that from conventional water extraction method at $100^{\circ}C$ as 23.2%, 22.5%, 21.2%. The secretion of $NO^-$ from macrophage showed $15.9\;{\mu}M$ on the R. coreanus extract from this process, which was higher than others. Prostaglandin $E_2$ ($PGE_2$) production from UV-induced human skin cells was also greatly decreased down to $510\;pg/m{\ell}$, compared to the control. From the results, we considered that the extracts from R. coreanus could be potent natural materials for skin anti-inflammation agent, and could be used as a potential anti-aging for the photo-damaged skin.

• 대한한방부인과학회지
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• 제20권4호
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• pp.56-73
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• 2007

Purpose: 이 실험은 골다공증의 치료약물로 자하거의 골질재흡수 억제효과를 검토하기 위하여 설계되었다. Methods: 자하거의 골질재흡수 효과를 확인하기 위하여 생쥐의 두개골 골모세포를 이용하여 Cyclooxygenase-1(COX-1), COX-2, $TGF-{\beta}$, $L-1{\beta}$, $TNF-{\alpha}$, IL-6, prostaglandin E2등의 활성화 정도를 측정하였으며, 골조직의 미세구조적 변화를 확인하였다. Results: 자하거는 $IL-1{\beta}$, $TNF-{\alpha}$, IL-6 또는 그 세가지의 조합에 의하여 유발된 PGE2의 생성 뿐만 아니라 COX-2 mRNA 수치도 감소시켰으나 COX-1 mRNA 수치에는 영향을 주지 않았다. 이로써 자하거는 시험관내에서 그리고 생체내에서 펩티드의 인산화를 억제함으로써 골의 재흡수를 저해하였다. 그리고 자하거는 생쥐에서 $IL-1{\beta}$에 의해 유발된 고칼슘혈증을 감소시켰고, 골의 재흡수를 저해하는 경로를 통하여 골에 대한 보호효과를 보여줌으로써 조기에 난소 절제한 쥐에서 골질감소와 미세구조적 변화를 부분적으로 방지하였다. 이러한 결과는 PGE2 생성에 대한 $IL-1{\beta}$, $TNF-{\alpha}$, IL-6사이의 상승효과는 COX-2의 유전자 발현이 증가한 결과이며 이러한 tyrosine kinase가 생쥐의 두개골 골모세포에서 COX-2의 신호전달에 관계한다는 것을 보여준다. Conclusion: 자하거가 생쥐의 두개골 골모세포에서 여러 신호전달물질의 활성화를 통하여 골질재흡수를 저해하는 특성을 확인함으로써 앞으로 골다공증의 예방과 치료에 대한 추가적인 임상연구가 필요할 것으로 사료된다.

• Journal of Oral Medicine and Pain
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• 제25권1호
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• pp.53-62
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• 2000

Bone marrow culture systems are widely used to differentiate osteoclast-like cells in vitro using several osteotropic hormones. In this study, we isolated and cultured the mouse bone marrow cells with or without some osteotropic hormones such as parathyroid hormone(PTH), prostaglandin $E_2(PGE_2)$ and $l,25(OH)_2-vitamin$ $D_3$(Vit. $D_3$). We confirmed the formation of osteoclast-like cells morphologically and functionally by the expression of tartrate-resistant acid phosphatase(TRAP) and by their capability to resorb dentin slices. We also studied the effects of transforming growth $factor-{\beta}(TGF-{\beta})$ and epidermal growth factor(EGF) on the Vit. $D_3-induced$ osteoclast-like cell formation. In control, a few multinucleated cells were formed whereas PTH and $PGE_2$ increased the number of multinucleated cells. PTH, $PGE_2$ and Vit. $D_3$ induced the formation of TRAP-positive multinucleated cells. After culture of mouse bone marrow cells on the dentin slices with or without osteotropic hormones, giant cells with diverse morphology were found on the dentin slices under the scanning electronmicroscopy. After removing the attached cells, resorption pits were identified on the dentin slices, and the shape of resorption pits was variable. EGF increased the osteoclast-like cell formation induced by Vit. $D_3$, however, $TGF-{\beta}$ showed biphasic effect, which at low concentration, increased and at high concentration, decreased the osteoclast-like cell formation induced by Vit. $D_3$.

• Preventive Nutrition and Food Science
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• 제17권1호
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• pp.22-28
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• 2012

Melaleuca leucadendron L. has been used as a tranquilizing, sedating, evil-dispelling and pain-relieving agent. We examined the effects of M. leucadendron L. extracts on oxidative stress and inflammation. M. leucadendron L. was extracted with methanol (MeOH) and then fractionated with chloroform ($CHCl_3$) and butanol (BuOH). Antioxidant activity of the MeOH extract and BuOH fraction were higher than that of both ${\alpha}$-tocopherol and butyrated hydroxytoluene (BHT). Total phenol content in the extracts of M. leucadendron L., especially the BuOH fraction, well correlated with the antioxidant activity. The anti-inflammatory activity of BuOH extracts were investigated by lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production, and cyclooxygenase-2 (COX-2) expression in RAW 264.7 macrophages. The BuOH fraction significantly inhibited LPS-induced NO and $PGE_2$ production. Furthermore, BuOH extract of M. leucadendron L. inhibited the expression of COX-2 and iNOS protein without an appreciable cytotoxic effect on RAW264.7 cells. The extract of M. leucadendron L. also suppressed the phosphorylation of inhibitor ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$) and its degradation associated with nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation. Furthermore, BuOH fraction inhibited LPS-induced NF-${\kappa}B$ transcriptional activity in a dose-dependent manner. These results suggested that M. leucadendron L. could be useful as a natural antioxidant and anti-inflammatory resource.

• 한국해양바이오학회지
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• 제12권1호
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• pp.29-39
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• 2020

In this study, we investigated the inhibitory potential of an ethanol extract of Carpomitra costata (EECC) (Stackhouse) Batters, a brown alga, against neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that EECC significantly suppressed the LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E₂, with no significant cytotoxic effects. EECC also inhibited the LPS-induced expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. In addition, EECC downregulated the LPS-induced expression and production of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β. In the mechanistic assessment of the antineuroinflammatory effects, EECC was found to inhibit the nuclear translocation and DNA binding of nuclear factor-kappa B (NF-κB) by disrupting the degradation of the κB-α inhibitor in the cytoplasm. Moreover, EECC effectively suppressed the enhanced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, as well as the binding of LPS to TLR4 in LPS-treated BV2 cells. Furthermore, EECC markedly reduced the LPS-induced generation of reactive oxygen species (ROS), demonstrating a strong antioxidative effect. Collectively, these results suggest that EECC repressed LPS-mediated inflammatory action in the BV2 microglia through the inactivation of NF-κB signaling by antagonizing TLR4 and/or preventing ROS accumulation. While further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant activity of EECC, the current findings suggest that EECC has a potential advantage in inhibiting the onset and treatment of neuroinflammatory diseases.

• Toxicological Research
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• 제29권3호
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• pp.195-201
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• 2013

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

• 생약학회지
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• 제37권4호
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• pp.235-240
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• 2006

We investigated the antioxidant activities such as DPPH radical scavenging capacity, xanthine oxidase inhibitory activity, and superoxide radical scavenging capacity of the aqueous EtOH extract and its solvent fractions of Artemisia scoparia. The ethyl acetate fraction showed high antioxidant activity, compared to positive controls such as ascorbic acid, butylated hydroxy anisole (BHA), trolox, and allopurinol in these assay systems. Moreover, we examined the inhibitory effect of solvent fractions of A. scoparia on the production of pro-inflammatory factors that the nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostaglandin E2 $(PGE_2)$ production activated with LPS $(1{\mu}g/ml)$ in murine macrophage cell line RAW264.7. The amounts of protein levels were determined by immunoblottting. Tn the sequential fractions of hexane and dichloromethane inhibited the NO and $PGE_2$ production and the protein level of iNOS and COX-2. These results suggest that A. scoparia may have anti-inflammatory activity through the antioxidant activity and inhibition of pro-inflammatory factors.