• 제목/요약/키워드: JAK3

검색결과 122건 처리시간 0.02초

Gamma Irradiation-reduced IFN-γ Expression, STAT1 Signals, and Cell-mediated Immunity

  • Han, Seon-Kyu;Song, Jie-Young;Yun, Yeon-Sook;Yi, Seh-Yoon
    • BMB Reports
    • /
    • 제35권6호
    • /
    • pp.583-589
    • /
    • 2002
  • The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon $\gamma$ (IFN-$\gamma$). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-$\gamma$-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-$\gamma$ mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.

POPs의 순환에 미치는 유기물 및 black carbon의 역할 (The Role of Organic Matter and Black Carbon on the Cycling of Persistent Organic Pollutants (POPs))

  • 남재작;홍석영;김계훈
    • Environmental Analysis Health and Toxicology
    • /
    • 제21권3호
    • /
    • pp.255-266
    • /
    • 2006
  • Soil organic matter (OM) is well documented for its capacity to retain persistent organic pollutants (POPs) and thus is important in dictating the environmental partitioning of POPs between media such as air, water, and soil. Black carbon (BC) is a small component of OM and exhibitt a 10$\sim$100 times greater sorption capacity of POPs than humified OM. Furthermore, due to the inherent long environmental life time of BC, a result of its resistance to physical and biological degradation, POPs can continue to accumulate in BC over a long period of time. The unique properties of BC have been of particular interest over the last 30 years and have resulted in broad research being conducted into its effects of POP cycling in atmospheric, oceanographic and soil matrices. The results of such studies have proved valuable In providing new research initiatives into the role of BC in the cycling of hydrophobic organic compounds (HOCs) as well as giving further insight into the long range atmospheric transport (LRAT) potential and subsequent risk assessment criteria for persistent organic pollutants (POPs). In this report, we introduce a novel study examining the relationships between BC and OM with respect to their POP sorption capacity and discuss the role of BC in influencing the environmental regulation of organic pollutants.

RAW264.7 대식세포에서 방사선에 의한 MCP-1 발현 기작 연구 (Study on the Mechanism of Radiation-induced MCP-1 Expression in RAW264.7 Macrophage Cells)

  • 진창현;박용대;최대성;정일윤
    • 방사선산업학회지
    • /
    • 제4권3호
    • /
    • pp.227-231
    • /
    • 2010
  • The purpose of this study was to investigate the expression mechanism of MCP-1 in gamma-irradiated RAW 264.7 macrophage cells. MCP-1 plays an important role in attracting monocyte to injured site at the early inflammation stage. However the production mechanism of MCP-1 by gamma-irradiation in RAW 264.7 macrophage cells was almost undiscovered. We found that MCP-1 was produced in RAW 264.7 macrophage cells by irradiation with 5 Gy. And these inceases were attenuated by specific inhibitors treatment, such as $NF-{\kappa}B$, JNK, ERK, JAK2, and Pyk2. These results indicate that radiation-induced MCP-1 production is mediated by MyD88- and TRIF-dependent pathways in RAW 264.7 macrophage cells. Furthermore, gamma-irradiation induced heme oxygenase-1 (HO-1) expression in RAW 264.7 macrophage cells. However this induction level was reduced before MCP-1 and $IFN-{\beta}$ production.

AZD1480 Can Inhibit the Biological Behavior of Ovarian Cancer SKOV3 Cells in vitro

  • Sun, Zhao-Ling;Tang, Ya-Juan;Wu, Wei-Guang;Xing, Jun;He, Yan-Fang;Xin, De-Mei;Yu, Yan-Li;Yang, Yang;Han, Ping
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제14권8호
    • /
    • pp.4823-4827
    • /
    • 2013
  • Objective: To study the mechanism of effects of AZD1480 on the SKOV3 ovarian cancer cell line. Methods: The MTT method was used to assess cellular proliferation, flow cytometry for cellular apoptosis, the scratch test to determine migration, transwell chamber assays to detect cellular invasion, plate clone experiments to detect the clone forming ability and Western blotting to determine p-STAT3 protein levels. Results: The proliferation rate, migration ability, invasiveness and the clone forming ability of SKOV3 cells were reduced after treatment with AZD1480, while apoptosis rate and chemotherapeutic susceptibility were increased. After treatment with AZD1480 plus cisplatin, the apoptosis rate increased significantly while the expression level of p-STAT3 protein was decreased. Conclusion: AZD1480 can inhibit the proliferation, invasion, metastasis and clone formation of SKOV3 cells, induce cellulsar apoptosis, increase the chemotherapeutic sensitivity and reduce the expression level of p-STAT3 protein.

The increasing hematopoietic effect of the combined treatment of Korean Red Ginseng and Colla corii asini on cyclophosphamide-induced immunosuppression in mice

  • Lee, Yuan Yee;Irfan, Muhammad;Quah, Yixian;Saba, Evelyn;Kim, Sung-Dae;Park, Seung-Chun;Jeong, Myung-Gyun;Kwak, Yi-Seong;Rhee, Man Hee
    • Journal of Ginseng Research
    • /
    • 제45권5호
    • /
    • pp.591-598
    • /
    • 2021
  • Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8+ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

Signaling Role of Adipocyte Leptin in Prostate Cell Proliferation Induced by Trichomonas vaginalis

  • Kim, Jung-Hyun;Han, Ik-Hwan;Shin, Su-Jin;Park, Sung-Yul;Chung, Hyo-Yeoung;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
    • /
    • 제59권3호
    • /
    • pp.235-249
    • /
    • 2021
  • Leptin is a type of adipokine mainly produced by adipocytes and reported to be overproduced in prostate cancer. However, it is not known whether it stimulates the proliferation of prostate cells. In this study, we investigated whether benign prostatic hyperplasia epithelial cells (BPH-1 cells) infected with Trichomonas vaginalis induced the proliferation of prostate cells via a leptin signaling pathway. To investigate the effect of crosstalk between adipocyte leptin and inflamed epithelial cell in proliferation of prostate cells, adipocytes 3T3-L1 cells were incubated in conditioned medium of BPH-1 cells infected with T. vaginalis (T. vaginalis-conditioned medium, TCM), and then the adipocyte-conditioned medium (ATCM) was identified to cause proliferation of prostate cells. BPH-1 cells incubated with live T. vaginalis released pro-inflammatory cytokines, and conditioned medium of these cells caused migration of adipocytes. When prostate stromal cells and BPH-1 cells were incubated with adipocyte conditioned medium containing leptin, their growth rates increased as did expression of the leptin receptor (known as OBR) and signaling molecules such as JAK2/STAT3, Notch and survivin. Moreover, blocking the OBR reduced this proliferation and the expression of leptin signaling molecules in response to ATCM. In conclusion, our findings show that inflamed BPH-1 cells infected with T. vaginalis induce the proliferation of prostate cells through leptin-OBR signaling. Therefore, it is likely that T. vaginalis contributes to prostate enlargement in BPH via adipocyte leptin released as a result of inflammation of the prostate.

The Genome-Wide Expression Profile of Saussurea lappa Extract on House Dust Mite-Induced Atopic Dermatitis in Nc/Nga Mice

  • Lim, Hye-Sun;Ha, Hyekyung;Shin, Hyeun-Kyoo;Jeong, Soo-Jin
    • Molecules and Cells
    • /
    • 제38권9호
    • /
    • pp.765-772
    • /
    • 2015
  • Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa's anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atoptic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa's properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and $IL20R{\beta}$ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not $IL20R{\beta}$ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.

Identification of Gene-based Potential Biomarkers for Cephalexin-induced Nephrotoxicity in Mice

  • Park, Han-Jin;Oh, Jung-Hwa;Hwang, Ji-Yoon;Lim, Jung-Sun;Jeong, Sun-Young;Kim, Yong-Bum;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
    • /
    • 제2권3호
    • /
    • pp.193-201
    • /
    • 2006
  • Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

영남지역 논토양에서 다핵방향족탄화수소 농도의 장기변동 (Long-term Changes in Polycyclic Aromatic Hydrocarbon Content of Paddy Soils in Youngnam area)

  • 남재작;홍석영;이희동;박창영;이상학
    • 한국토양비료학회지
    • /
    • 제40권3호
    • /
    • pp.196-200
    • /
    • 2007
  • 영남농업연구소에 보관된 토양 시료의 분석결과 밀양지역 논토양에서의 PAHs 함량 1978년 이후 지속적으로 감소되고 있는 것으로 나타났다. 1978년에 $200{\mu}g\;kg^{-1}$을 넘어서 1980년에 최고농도($237{\mu}g\;kg^{-1}$)에 달하였으나, 이후 지속적으로 감소하여 2001년에는 $100{\mu}g\;kg^{-1}$ 수준까지 감소하였다. 이상의 결과는 PAHs의 발생원이 적은 지역의 농경지에서는 1980년대 이후 대체적으로 PAHs의 농도가 감소하고 있고, 오염물질(PAHs)의 대기이동에 의한 토양오염의 우려가 비교적 낮다는 것을 시사한다.

Genetic Variants in Interleukin-2 and Risk of Lymphoma among Children in Korea

  • Song, Nan;Han, So-Hee;Lee, Kyoung-Mu;Choi, Ji-Yeob;Park, Sue-K;Jeon, Su-Jee;Lee, Yun-Hee;Ahn, Hyo-Seop;Shin, Hee-Young;Kang, Hyoung-Jin;Koo, Hong-Hoe;Seo, Jong-Jin;Choi, Ji-Eun;Kang, Dae-Hee
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권2호
    • /
    • pp.621-623
    • /
    • 2012
  • To estimate the genetic susceptibility for childhood lymphoma, we conducted an association study for 23 cases and 148 controls. Total 1536 tag single nucleotide polymorphisms (SNPs) were selected in 138 candidate gene regions related to immune responses, apoptosis, the cell cycle, and DNA repair. Twelve SNPs were significantly associated with the risk of lymphoma ($P_{trend}$ <0.05) in six genes ($IL1RN$, $IL2$, $IL12RB1$, $JAK3$, $TNFRSF13B$, and $XRCC3$). The most significant association was seen for $IL2$ variant rs2069762 ($OR_{TG+GG}$ vs. TT=3.43 (1.29-9.11), $P_{trend}$=0.002, min$P$=0.005). These findings suggest that common genetic variants in $IL2$ might play a role in the pathogenesis of childhood lymphoma.