Role of P38 MAPK, AP-1, and NF-κB in interleukin-1β-induced IL-8 expression in human vascular smooth muscle cells

被引:86
作者
Jung, YD
Fan, F
McConkey, DJ
Jean, ME
Liu, WB
Reinmuth, N
Stoeltzing, O
Ahmad, SA
Parikh, AA
Mukaida, N
Ellis, LM
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[2] Chonnam Natl Univ, Res Inst Med Sci, Kwangju 501190, South Korea
[3] Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA
[4] Kanazawa Univ, Canc Res Inst, Div Mol Bioregulat, Kanazawa, Ishikawa 9200934, Japan
关键词
interleukin-1; beta; interleukin-8; AP-1; mitogen-activated protein kinase; NF-kappa B;
D O I
10.1006/cyto.2002.1034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin (IL)-1 modulates the expression of various genes in normal and tumor cells. We investigated the molecular mechanisms underlying IL-1beta-induced expression of IL-8 mRNA and protein in human vascular smooth muscle cells (hVSMCs). P38 mitogen-activated protein kinase (MAPK) was activated after 5 min of IL-1beta treatment, whereas the extracellular signal-regulated kinases, the c-jun amino-terminal kinases, and protein kinase B/Akt were not activated by IL-1beta. IL-1beta induced activation of a full-length IL-8 promoter-reporter construct. Deletional mutagenesis localized the IL-1beta-responsive domains to two regions (- 133 to - 98 and - 85 to - 50) that contain consensus binding sites for activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), respectively. Site-directed mutagenesis of the 133-bp minimal promoter confirmed that these sites were required for promoter activity. Electrophoretic mobility shift assays confirmed that IL-1beta increased AP-1 and NF-kappaB DNA-binding activities in a time-dependent manner. S13203580, a specific P38 MAPK inhibitor, partially blocked IL-10 induction of IL-8 MRNA, IL-8 promoter activity, and AP-1 nuclear extract binding but not NF-kappaB DNA binding. Our data demonstrate that AP-1 and NF-kappaB are essential transcription factors for IL-IP-induced IL-8 gene expression in hVSMCs. P38 MAPK is involved in inducing IL-8 gene transcription via AP-1 activation in hVSMCs. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:206 / 213
页数:8
相关论文
共 29 条
[1]  
Akagi Y, 1998, CANCER RES, V58, P4008
[2]   Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice [J].
Arenberg, DA ;
Kunkel, SL ;
Polverini, PJ ;
Glass, M ;
Burdick, MD ;
Strieter, RM .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (12) :2792-2802
[3]  
BAGGIOLINI M, 1994, ADV IMMUNOL, V55, P97
[4]  
Barthelman M, 1998, CANCER RES, V58, P711
[5]   APL/JUN FUNCTION IS DIFFERENTIALLY INDUCED IN PROMOTION-SENSITIVE AND RESISTANT JB6 CELLS [J].
BERNSTEIN, LR ;
COLBURN, NH .
SCIENCE, 1989, 244 (4904) :566-569
[6]   Cellular differentiation causes a selective down-regulation of interleukin (IL)-1β-mediated NF-κB activation and IL-8 gene expression in intestinal epithelial cells [J].
Böcker, U ;
Schottelius, A ;
Watson, JM ;
Holt, L ;
Licato, LL ;
Brenner, DA ;
Sartor, RB ;
Jobin, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (16) :12207-12213
[7]   AU-RICH ELEMENTS - CHARACTERIZATION AND IMPORTANCE IN MESSENGER-RNA DEGRADATION [J].
CHEN, CYA ;
SHYU, AB .
TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (11) :465-470
[8]   HOW MAP KINASES ARE REGULATED [J].
COBB, MH ;
GOLDSMITH, EJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (25) :14843-14846
[9]   Biologic basis for interleukin-1 in disease [J].
Dinarello, CA .
BLOOD, 1996, 87 (06) :2095-2147
[10]   ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE [J].
FOLKMAN, J .
NATURE MEDICINE, 1995, 1 (01) :27-31