IL-17 Promotes Angiogenic Factors IL-6, IL-8, and Vegf Production via Stat1 in Lung Adenocarcinoma

被引:95
作者
Huang, Qi [1 ]
Duan, Limin [1 ]
Qian, Xin [2 ]
Fan, Jinshuo [1 ]
Lv, Zhilei [1 ]
Zhang, Xiuxiu [1 ]
Han, Jieli [1 ]
Wu, Feng [1 ]
Guo, Mengfei [1 ]
Hu, Guorong [1 ]
Du, Jiao [3 ]
Chen, Caiyun [4 ]
Jin, Yang [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Key Lab Pulm Dis,Minist Hlth,Dept Resp & Crit Car, 1277 Jiefang Ave, Wuhan 430022, Peoples R China
[2] Hubei Univ Med, Taihe Hosp, Dept Resp Med, 32 South Renmin Rd, Shiyan 442000, Hubei, Peoples R China
[3] Xiamen Univ, Zhongshan Hosp, 201-209 Hubin Rd, Xiamen 361004, Fujian, Peoples R China
[4] First Hosp Xian City, Dept Resp Med, Xian 710002, Shanxi, Peoples R China
基金
高等学校博士学科点专项科研基金; 中国国家自然科学基金;
关键词
CANCER STATISTICS; TUMOR PROGRESSION; TH17; CELLS; EXPRESSION; INTERLEUKIN-17; PATHWAY; GROWTH; INFLAMMATION; METASTASIS; CYTOKINES;
D O I
10.1038/srep36551
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Inflammation and angiogenesis are two hallmarks of carcinoma. The proinflammatory cytokine interleukin-17 (IL-17) facilitates angiogenesis in lung cancer; however, the underlying mechanism is not fully understood. In this study, tumour microvessel density (MVD) was positively associated with IL-17, interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial cell growth factor (VEGF) expression in human lung adenocarcinoma tissues, and it was increased in tumour tissues of A549-IL-17 cell-bearing nude mice. Importantly, positive correlations were also detected between IL-17 expression and IL-6, IL-8 and VEGF expression in human lung adenocarcinoma tissues. Furthermore, IL-6, IL-8 and VEGF production, as well as STAT1 phosphorylation, were increased in tumour tissues of A549-IL-17 cell-bearing nude mice in vivo and in A549 and H292 cells following IL-17 stimulation in vitro. In addition, STAT1 knockdown using an inhibitor and siRNA attenuated the IL-17-mediated increases in IL-6, IL-8 and VEGF expression in A549 and H292 cells. In conclusion, IL-17 may promote the production of the angiogenic inducers IL-6, IL-8 and VEGF via STAT1 signalling in lung adenocarcinoma.
引用
收藏
页数:12
相关论文
共 42 条
[21]   IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma [J].
Liu, Jiankun ;
Duan, Yuzhong ;
Cheng, Xiaoming ;
Chen, Xi ;
Xie, Wei ;
Long, Haixia ;
Lin, Zhihua ;
Zhu, Bo .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 407 (02) :348-354
[22]   Interleukin-17 and Prostaglandin E2 Are Involved in Formation of an M2 Macrophage-Dominant Microenvironment in Lung Cancer [J].
Liu, Lunxu ;
Ge, Dongxia ;
Ma, Lin ;
Mei, Jiandong ;
Liu, Sen ;
Zhang, Qiuyang ;
Ren, Fuqiang ;
Liao, Hu ;
Pu, Qiang ;
Wang, Tao ;
You, Zongbing .
JOURNAL OF THORACIC ONCOLOGY, 2012, 7 (07) :1091-1100
[23]   Targeting IL-17and TH17 cells in chronic inflammation [J].
Miossec, Pierre ;
Kolls, Jay K. .
NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (10) :763-776
[24]   Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer [J].
Miyahara, Yoshihiro ;
Odunsi, Kunle ;
Chen, Wenhao ;
Peng, Guangyong ;
Matsuzaki, Junko ;
Wang, Rong-Fu .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (40) :15505-15510
[25]   Protumor vs Antitumor Functions of IL-17 [J].
Murugaiyan, Gopal ;
Saha, Bhaskar .
JOURNAL OF IMMUNOLOGY, 2009, 183 (07) :4169-4175
[26]   IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis [J].
Numasaki, M ;
Watanabe, M ;
Suzuki, T ;
Takahashi, H ;
Nakamura, A ;
McAllister, F ;
Hishinuma, T ;
Goto, J ;
Lotze, MT ;
Kolls, JK ;
Sasaki, H .
JOURNAL OF IMMUNOLOGY, 2005, 175 (09) :6177-6189
[27]   Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer [J].
Pan, Bo ;
Shen, Jing ;
Cao, Jingyan ;
Zhou, Yongxu ;
Shang, Lihua ;
Jin, Shi ;
Cao, Shoubo ;
Che, Dehai ;
Liu, Fang ;
Yu, Yan .
SCIENTIFIC REPORTS, 2015, 5
[28]   Understanding Th17 cells through systematic genomic analyses [J].
Peters, Anneli ;
Yosef, Nir .
CURRENT OPINION IN IMMUNOLOGY, 2014, 28 :42-48
[29]   Association of IL-8 gene polymorphisms with non small cell lung cancer in Tunisia: A case control study [J].
Rafrafi, Ahlem ;
Chahed, Besma ;
Kaabachi, Safa ;
Kaabachi, Wajih ;
Maalmi, Haifa ;
Hamzaoui, Kamel ;
Sassi, Faycal Haj .
HUMAN IMMUNOLOGY, 2013, 74 (10) :1368-1374
[30]   IL-17A is a central regulator of lung tumor growth [J].
Reppert, Sarah ;
Koch, Sonja ;
Finotto, Susetta .
ONCOIMMUNOLOGY, 2012, 1 (05) :783-785