• Title, Summary, Keyword: ${\kappa}Bp65$

Search Result 24, Processing Time 0.163 seconds

USP15 inhibits multiple myeloma cell apoptosis through activating a feedback loop with the transcription factor NF-κBp65

  • Zhou, Lili;Jiang, Hua;Du, Juan;Li, Lu;Li, Rong;Lu, Jing;Fu, Weijun;Hou, Jian
    • Experimental and Molecular Medicine
    • /
    • v.50 no.11
    • /
    • pp.11.1-11.12
    • /
    • 2018
  • USP15 has been shown to stabilize transcription factors, to be amplified in many cancers and to mediate cancer cell survival. However, the underlying mechanism by which USP15 regulates multiple myeloma (MM) cell proliferation and apoptosis has not been established. Here, our results showed that USP15 mRNA expression was upregulated in MM patients. USP15 silencing induced MM cell proliferation inhibition, apoptosis, and the expression of nuclear and cytoplasmic NF-${\kappa}Bp65$, while USP15 overexpression exhibited an inverse effect. Moreover, in vivo experiments indicated that USP15 silencing inhibited MM tumor growth and NF-${\kappa}Bp65$ expression. PDTC treatment significantly inhibited USP15 overexpression-induced cell proliferation, apoptosis inhibition, and NF-${\kappa}Bp65$ expression. USP15 overexpression promoted NF-${\kappa}Bp65$ expression through inhibition of its ubiquitination, whereas NF-${\kappa}Bp65$ promoted USP15 expression as a positive regulator. Taken together, the USP15-NF-${\kappa}Bp65$ loop is involved in MM tumorigenesis and may be a potential therapeutic target for MM.

The effect of Gagamchunggan-tang on lipopolysaccharide-induced expression of $NF{\kappa}-B$ downstream genes in HepG2 cell (Lipopolysaccharide로 유발된 HepG2 세포의 염증반응에 대한 가감청간탕의 효과에 대한 연구)

  • Kim Sung-Hwan;Seo Sang-Ho;Hong Sang-Hoon
    • The Journal of Internal Korean Medicine
    • /
    • v.24 no.1
    • /
    • pp.113-122
    • /
    • 2003
  • Objective : The aim of this study was to evaluate the efficacy of Gagamchunggan-tang on anti-inflammation reaction with lipopolysaccharide (LPS)-induced HepG2 cell. Method : We examined the effects of the Gagamchunggan-tang, a traditional drug for liver inflammation, on the process of lipopolysaccharide(LPS)-induced nuclear factor-${\kappa}Bp65(NF-{\kappa}Bp65)$ activation in HepG2 cell. SDS-PAGE, Western blotting, Immunofluorescence staining were studied. Results : Immunoblot analysis showed that the level of nucleic $NF-{\kappa}Bp65$ was rapidly up-regulated and cytosolic inhibitory $I-{\kappa}B{\alpha}$ was down-regulated by LPS challenge. While Gagamchunggan-tang inhibited an increase of $NF-{\kappa}Bp65$ and degradation of $I-{\kappa}B{\alpha}$ in HepG2 cell. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-${\alpha}(TNF-{\alpha})$, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2 (COX-2), are repressed by Gagamchunggan-tang. It may be concluded that Gagamchunggan-tang attenuates the progress of LPS-induced inflammation by reduction of $NF-{\kappa}Bp65$ activation. Conclusion : The Gagamchunggan-tang would be useful as a therapeutic agent for endotoxin-induced liver disease.

  • PDF

Kamgil-Tang attenuates lipopolysaccharide-induced NF-${\kappa}$B activation in RAW 264.7 cell and acute lung injury in rats

  • Park, Dong-Il;Kim, Do-Hyun;Choi, Byung-Tae
    • Journal of Life Science
    • /
    • v.10 no.2
    • /
    • pp.55-60
    • /
    • 2000
  • We examined the effects of Kamgil-Tang on the process of lipopolysaccharide (LPS)-induced unclear factor (NF)-${\kappa}$ Bp65 and inhibitory (I)-${\kappa}$ B${\alpha}$ alteration in RAW 264.7 cell and acute lung injury in rats. Immunoblot analysis showed that LPS-induced degradation of I-${\kappa}$ B${\alpha}$ in RAW 264.7 was inhibited by pretreatment of Kamgil-Tang. The total cells of bronchoalveolar lavage fluid by LPS challenge markedly decreased in the Kamgil-Tang pretreatment rats. Kamgil-Tang pretreatment caused also a decline in neutrophils infiltration into interstitium of the lung. In the alveolar macrophages and neutrophils, decreased NF-${\kappa}$ Bp65 and inducible nitric oxide synthase and increased I-${\kappa}$ B${\alpha}$ immunoreaction were detected in Kamgil-Tang pretreated rats compared with LPS alone treated ones. It may be concluded that Kamgil-Tang attenuates the development of LPS-induced inflammation by reduction of NF-${\kappa}$ Bp65 activation and neutrophil-mediated acute lung injury. Kamgil-Tang would be useful as a therapeutic agent for endotoxin-induced lung disease.

  • PDF

The Effects of Platycodi Radix on the Induction of LPS and the Activation of $NF-{\kappa}Bp$, the Lung Disease of White Rats

  • Kim Hyun-Joong;Park Dong-Il;Kim Won-Il
    • The Journal of Korean Medicine
    • /
    • v.26 no.1
    • /
    • pp.18-25
    • /
    • 2005
  • Objective & Methods: We examined the effects of Platycodi radix on the process of lipopolysaccharide (LPS)-induced nuclear factor $NF-{\kappa}Bp65$ and inhibitory $(I)-{\kappa}B{\alpha}$ alteration in RAW 264.7 cells and acute lung injury in rats. Results: Immunoblot analysis showed that LPS-induced degradation of $I-{\kappa}B{\alpha}$ in RAW 264.7 was inhibited by pretreatment of Platycodi radix. The total cells of bronchoalveolar lavage fluid by LPS challenge markedly decreased in the Platycodi radix pretreatment rats. Platycodi radix pretreatment also caused a decline in neutrophils infiltration into interstitium of the lung. In the alveolar macrophages and neutrophils, decreased $NF-{\kappa}Bp65$ and inducible nitric oxide synthase and increased $I-{\kappa}B{\alpha}$ immunoreaction were detected in Platycodi radix pretreated rats compared with LPS alone treated ones. Conclusion : It may be concluded that Platycodi radix attenuates the development of LPS-induced inflammation by reduction of $NF-{\kappa}Bp65$ activation and neutrophil-mediated acute lung injury. Platycodi radix would be useful as a therapeutic agent for endotoxin-induced lung disease.

  • PDF

Anti-Proliferation Effects and Molecular Mechanisms of Action of Tetramethypyrazine on Human SGC-7901 Gastric Carcinoma Cells

  • Ji, Ai-Jun;Liu, Sheng-Lin;Ju, Wen-Zheng;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.8
    • /
    • pp.3581-3586
    • /
    • 2014
  • Aim: To investigate the effects of tetramethypyrazine (TMP) on proliferation and apoptosis of the human gastric carcinoma cell line 7901 and its possible mechanism of action. Methods: The viability of TMP-treated 7901 cells was measured with a 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and cell apoptosis was analyzed by flow cytometry. The distribution of cells in different phases of cell cycle after exposure of TMPs was analyzed with flow cytometry. To investigate the molecular mechanisms of TMP-mediated apoptosis, the expression of NF-${\kappa}Bp65$, cyclinD1 and p16 in SGC-7901 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Results: TMP inhibited the proliferation of human gastric carcinoma cell line 7901 in dose and time dependent manners. Cell growth was suppressed by TMP at different concentrations (0.25, 0.5, 1.0, 2.0 mg/ml), the inhibition rate is 0.46%, 4.36%, 14.8%, 76.1% (48h) and 15.5%, 18.5%, 41.2%, 89.8% (72h) respectively. When the concentration of TMPs was 2.0mg/ml, G1-phase arrest in the SGC-7901 cells was significant based on the data for cell cycle distribution. RT-PCR demonstrated that NF-${\kappa}Bp65$ and cyclin D1 mRNA expression was significantly down-regulated in 7901 cells treated with 2.0 mg/ml TMP for 72h (p<0.05), while the p16 mRNA level was up-regulated (p<0.05). The protein expression of NF-${\kappa}Bp65$ and cyclin D1 decreased gradually with the increase in TMP concentration, compared with control cells (p<0.05), while expression of protein p16 was up-regulated (p<0.01). Conclusion: TMP exhibits significant anti-proliferative and pro-apoptotic effects on the human gastric carcinoma cell line SGC-7901. NF-${\kappa}Bp65$, cyclinD1 and p16 may also play important roles in the regulation mechanisms.

Induction of Mac-2BP by nerve growth factor is regulated by the PI3K/Akt/NF-κB-dependent pathway in the HEK293 cell line

  • Park, Yuk-Pheel;Choi, Seung-Chul;Kim, Bo-Yeon;Kim, Jong-Tae;Song, Eun-Young;Kang, Seong-Ho;Yoon, Do-Young;Paik, Sang-Gi;Kim, Kwang-Dong;Kim, Jong-Wan;Lee, Hee-Gu
    • BMB Reports
    • /
    • v.41 no.11
    • /
    • pp.784-789
    • /
    • 2008
  • Mac-2BP is a ligand of the galectin family that has been suggested to affect tumor proliferation and metastasis formation. We assessed Mac-2BP expression at the transcriptional and translational levels to evaluate nerve growth factor (NGF)-induced Mac-2BP expression. A time kinetic analysis using reverse transcription-polymerase chain reaction showed that NGF-induced Mac-2BP transcript levels were 4-5 times higher than in controls. Mac-2BP enzyme-linked immunosorbent assay and immuno-fluorescence staining showed a 2-3-fold increase in intracellular and secreted Mac-2BP as a result of NGF stimulation. This increase was regulated by Akt activation and NF-${\kappa}B$ binding. p65 and p50-NF-${\kappa}B$ are major transcriptional factors in the Mac-2BP promoter region, and were shown to be regulated in accordance with the Akt activation states. Collectively, these results suggest that NGF induces Mac-2BP expression via the PI3K/Akt/NF-${\kappa}B$ pathway.

The IRF2BP2-KLF2 axis regulates osteoclast and osteoblast differentiation

  • Kim, Inyoung;Kim, Jung Ha;Kim, Kabsun;Seong, Semun;Kim, Nacksung
    • BMB Reports
    • /
    • v.52 no.7
    • /
    • pp.469-474
    • /
    • 2019
  • Kruppel-like factor 2 (KLF2) has been implicated in the regulation of cell proliferation, differentiation, and survival in a variety of cells. Recently, it has been reported that KLF2 regulates the p65-mediated transactivation of $NF-{\kappa}B$. Although the $NF-{\kappa}B$ pathway plays an important role in the differentiation of osteoclasts and osteoblasts, the role of KLF2 in these bone cells has not yet been fully elucidated. In this study, we demonstrated that KLF2 regulates osteoclast and osteoblast differentiation. The overexpression of KLF2 in osteoclast precursor cells inhibited osteoclast differentiation by downregulating c-Fos, NFATc1, and TRAP expression, while KLF2 overexpression in osteoblasts enhanced osteoblast differentiation and function by upregulating Runx2, ALP, and BSP expression. Conversely, the downregulation of KLF2 with KLF2-specific siRNA increased osteoclast differentiation and inhibited osteoblast differentiation. Moreover, the overexpression of interferon regulatory protein 2-binding protein 2 (IRF2BP2), a regulator of KLF2, suppressed osteoclast differentiation and enhanced osteoblast differentiation and function. These effects were reversed by downregulating KLF2. Collectively, our data provide new insights and evidence to suggest that the IRF2BP2/KLF2 axis mediates osteoclast and osteoblast differentiation, thereby affecting bone homeostasis.

Immunohistochemical Study on the Inflammation-related Proteins in the Ankle Joint of Complete Freund's Adjuvant-injected Rat by Electroacupuncture Stimulation (전침에 의한 Complete Freund's Adjuvant유발 관절염모델의 거퇴관절 내 염증관련 단백질에 대한 면역조직화학적 연구)

  • Park, In-Bum;Choi, Byung-Tae;Ahn, Chang-Beohm
    • Journal of Acupuncture Research
    • /
    • v.22 no.4
    • /
    • pp.55-63
    • /
    • 2005
  • 목적 : 만성 염증성 질환에 대한 전침효과를 알아보기 위해 complete Freund's adjuvant (CA) 유발 관절염 모델에서 염증관련 단백질의 변화를 살펴보았다. 방법 : Sprague-Dawley계 흰쥐의 족부에 CFA를 주사한 다음 3일 간격으로 2 Hz, 15 Hz 및 120 Hz 전침 자극을 주며 부종 형성여부를 plethysmometer로 측정하여 판정하였으며 30일 째 거퇴관절을 취하여 4% paraformaldehyde에 고정하고 EDTA용액에서 탈회시켜 파라핀연속 절편을 얻어 $NF-{\kappa}B$를 비롯한 5종의 염증관련 단백질의 발현을 면역조직화학적으로 살펴보았다. 결과 : 관절연골내 면역반응 중 연골기질은 반응이 없거나 약하고 연골세포는 $NF-{\kappa}Bp65,\;I-{\kappa}B{\alpha},\;iNOS$반응이 강하며 특히 유리연골층에서 더 현저하였으나 염증 및 전침자극에 따른 변화는 없었다. 관절낭에서 면역반응을 살펴보면 염증유발시 활액세포의 면역반응세포는 $I-{\kappa}B{\alpha}$가 감소한 반면 iNOS, $IL-1{\beta}$는 증가하며 특히 iNOS 증가가 현저하였으며 전침자극에 의해 iNOS가 감소하였다. 활액막조직에서 모든 면역반응이 증가하며 특히 $NF-{\kappa}Bp65,\;I-{\kappa}B{\alpha},\;iNOS$ 반응이 현저한데 전침자극에 의해 $IL-1{\beta}$를 제외한 모든 반응이 감소하였다. 결론 : 만성 염증성 동물모델의 거퇴관절 내 염증관련 단백질은 관절연골보다 관절낭에서 큰 변화를 보이며 전침처치에 의해 이들 단백질 발현이 억제되는 것으로 보아 전침이 만성 염증성 질환에 효과적임을 알 수 있다.

  • PDF

Anti-inflammatory Effects of Gastrodia elata Extract in Lipopolysaccharide-stimulated BV-2 Microglia Cell

  • Heo, Young Hyun;Choi, Na Hyun;Seo, Young Kyung;Jang, Ji Yeon;Lee, Jun Hyuk;Kim, Jae Kyu;Choi, Byung Tae
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.26 no.5
    • /
    • pp.738-744
    • /
    • 2012
  • Gastrodia elata Blume is used for a variety of purposes including treatment of inflammation in the Korean medicine. The present study investigated whether the G. elata extracts have the anti-inflammatory effect on lipopolysaccharide(LPS)-stimulated BV-2 microglia cells. G. elata extracts showed an anti-inflammatory effects in the morphological and nitric oxide(NO) analysis, especially in hexane extract. So we investigated the hexane extract from G. elata in the following experiments. Hexane extract significantly inhibited the secretion of NO with protein level of inducible nitric oxide synthase in LPS-stimulated BV2 microglia cells. Hexane extract also inhibited LPS-stimulated inflammatory responses involving the degradation of cytosolic inhibitory(I)-${\kappa}B{\alpha}$ and the translocation of nuclear factor(NF)-${\kappa}Bp65$ to nucleus in LPS-stimulated BV-2 microglia cells by morphological analysis. Western blot analyse confirmed that I-${\kappa}B{\alpha}$ and NF-${\kappa}Bp65$ showed a similar pattern as morphological analysis. Our results suggest that G. elata extracts, especially hexane extract, may act as a therapeutic agent for inflammatory disease in the central nervous system through a selective regulation of NO production and NF-${\kappa}B$ activation.

Inhibitory Effects of Ecklonia cava Ethanol Extracts against TNF-α/IFN-γ-Induced Inflammation in Human Keratinocytes (피부각질형성세포에서 TNF-α/IFN-γ로 유도된 염증반응에 대한 감태 에탄올 추출물의 억제 효과)

  • Kang, Nalae;Han, Eui Jeong;Park, Soo Yeon;Jee, Youngheun;Jeon, You-Jin;Ahn, Chang Bum;Ahn, Ginnae
    • Journal of Chitin and Chitosan
    • /
    • v.22 no.2
    • /
    • pp.82-88
    • /
    • 2017
  • In this study, we investigated inhibitory effects of Ecklonia cava ethanol extract (ECE) against tumor necrosis factor $(TNF)-{\alpha}$/interferon $(IFN)-{\gamma}$-induced inflammation in HaCaT, a human keratinocytes. First of all, we identified that ECE did not show cytotoxicities at the used all concentrations. Also, ECE reduced the expression levels of inflammatory cytokines such as interleukin $(IL)-1{\beta}$, IL-4, IL-6, $IFN-{\gamma}$ and $TNF-{\alpha}$, compared to the only $TNF-{\alpha}/IFN-{\gamma}$-stimulated cells. In addition, the expression level of an inflammatory chemokine such as macrophage-derived chemokine (MDC) were decreased by the treatment of ECE in $TNF-{\alpha}/IFN-{\gamma}$-stimulated HaCaT keratinocytes. Furthermore, ECE suppressed the activation of nuclear factor $(NF)-{\kappa}Bp65$ by regulating the phosphorylation of $I{\kappa}B-{\alpha}$ and $NF-{\kappa}B$. From these results, we indicated that ECE exerts the anti-inflammatory effects by suppressing the expression of $TNF-{\alpha}/IFN-{\gamma}$-stimulated chemokines and pro-inflammatory molecules via a blockage of $NF-{\kappa}B$ activation in HaCaT keratinocytes. Our results suggest the preventive potential of ECE as a natural material for the treatment of inflammatory skin diseases.