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NF-κB signaling regulates cell-autonomous regulation of CXCL10 in breast cancer 4T1 cells
진원종,김봉준,김다롱,추해영박,김홍희,하현일,이장희 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells. Treatment of 4T1 cells with CXCL10 increased the expression of P65, a subunit of the NF-κB pathway, via activation of the NF-κB transcriptional activity. Ectopic overexpression of P65 increased CXCL10 secretion and blunted JN-2-induced suppression of CXCL10 secretion, whereas overexpression of IκBα suppressed CXCL10 secretion. These results indicate that the CXCL10/CXCR3 axis creates a positive feedback loop through the canonical NF-κB signaling pathway in 4T1 cells. In addition, treatment of osteoblasts with conditioned medium from JN-2-treated 4T1 cells inhibited the expression of RANKL, a crucial cytokine for osteoclast differentiation, which resulted in an inhibitory effect on osteoclast differentiation in the co-culture system of bone marrowderived macrophages and osteoblasts. Direct intrafemoral injection of 4T1 cells induced severe bone destruction; however, this effect was suppressed by the CXCR3 antagonist via downregulation of P65 expression in an animal model. Collectively, these results suggest that the CXCL10/CXCR3-mediated NF-κB signaling pathway plays a role in the control of autonomous regulation of CXCL10 and malignant tumor properties in breast cancer 4T1 cells.
충전 및 합성조건 변화에 따른 콘크리트 충전강관 거더의 휨거동에 관한 연구
진원종(Chin Won Jong),강재윤(Kang Jae Yoon),최은석(Choi Eun Suk),이정우(Lee Jung Woo) 대한토목학회 2009 대한토목학회논문집 A Vol.29 No.2A
이 연구에서는 CFT부재를 거더로 사용하는 신형식 강합성 교량 시스템 개발을 최종목표로 하고, CFT부재의 휨거동 특성을 규명하기 위한 부재실험을 수행하였다. 실험체는 충전재 강도 및 합성조건 변화 등 설계에 영향을 미치는 주요 매개 변수를 고려하여 제작하였고, 휨재하 실험의 결과분석을 통해 CFT부재가 갖는 내력성능을 효율적으로 설계에 반영하기 위한 방안을 고찰하였다. 충전강관은 중공강관에 비해 휨강도 및 연성이 크게 증가함을 확인할 수 있었으며, 콘크리트의 취성적 재료 특성이 강관의 구속효과로 보완되는 결과를 확인하였다. 내부 전단연결재를 둠으로써 충전재와 강관 사이의 미끄러짐을 억제하여 완전합성단면으로 거동하였고, 기형 전단연결재의 보강재 효과가 휨내력 증가에 다소 기여하고 있음을 알 수 있었다. A new bridge system described in this paper uses concrete-filled steel tube (CFT) girders as a replacement for conventional girders. Experimental investigations were carried out to comprehend the flexural behavior of CFT girder. Specimens were manufactured considering several parameters such as the strength of filling material, the eventual presence and number of inner shear connectors to evaluate the bending bearing capacity of CFT girder. The experimental investigation consisted of designing and constructing a test specimen and loading it to collapse in bending to check the applicability of the system. Test results showed that concrete filled steel tube girders have good ductility and maintain their strength up to the end of the loading. The stiffening effect of the ㄱ, -shaped perfobond rib is determined to contribute relatively to the increase of the bending bearing capacity.