Induction of E-selectin expression by double-stranded RNA and TNF-α is attenuated in murine aortic endothelial cells derived from double-stranded RNA-activated kinase (PKR)-null mice

被引:20
作者
Bandyopadhyay, SK
de la Motte, CA
Williams, BRG
机构
[1] Cleveland Clin Fdn, Dept Canc Biol, Lerner Res Inst, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Dept Urol, Lerner Res Inst, Cleveland, OH 44195 USA
[3] Cleveland Clin Fdn, Dept Colorectal Surg, Lerner Res Inst, Cleveland, OH 44195 USA
关键词
D O I
10.4049/jimmunol.164.4.2077
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The adherence of leukocytes on the endothelium is mediated in part by the transient expression of the E-selectin adhesion molecule. Because we have previously shown that the dsRNA-activated kinase PKR mediates dsRNA induction of NF-kappa B, we used murine aortic endothelial (MuAE) cells isolated from wild-type and PKR null mice to investigate the role of PKR in the induction of E-selectin expression by dsRNA (pIC) and TNF-alpha. E-selectin mRNA and protein expression was inducible by both pIC and TNF-alpha in wild-type MuAE cells, whereas induction of E-selectin expression by these agents was defective in PKR-null MuAE cells. Induction of E-selectin promoter activity and NF-kappa B DNA binding activity were substantially reduced in pIC- or TNF-alpha-treated PKR-null cells, indicating a role for PKR in both pIC and TNF-alpha induction of E-selectin via an NF-kappa B-dependent pathway. In PKR-null cells, pIC-mediated degradation of I kappa B beta is deficient. Activation of this pathway requires the PKR-dependent degradation of the I kappa B beta protein. Moreover, both phosphorylated and unphosphorylated activating transcription factor 2 DNA-binding activities were reduced in PKR-null aortic endothelial cells. These results indicate that the PKR is required for full activation of E-selectin expression by pIC and TNF-alpha in primary mouse aortic endothelial cells identifying activating transcription factor 2 as a new target for PKR-dependent regulation and suggest a role for PKR in leukocyte adhesion. The Journal of Immunology, 2000, 164: 2077-2083.
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页码:2077 / 2083
页数:7
相关论文
共 70 条
[1]  
AUSUBEL FM, CURRENT PROTOCOLS MO, V1
[2]   Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling [J].
Balachandran, S ;
Kim, CN ;
Yeh, WC ;
Mak, TW ;
Bhalla, K ;
Barber, GN .
EMBO JOURNAL, 1998, 17 (23) :6888-6902
[3]   TRANSCRIPTIONAL INDUCTION BY DOUBLE-STRANDED-RNA IS MEDIATED BY INTERFERON-STIMULATED RESPONSE ELEMENTS WITHOUT ACTIVATION OF INTERFERON-STIMULATED GENE FACTOR-3 [J].
BANDYOPADHYAY, SK ;
LEONARD, GT ;
BANDYOPADHYAY, T ;
STARK, GR ;
SEN, GC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (33) :19624-19629
[4]   Mechanisms of disease - Nuclear factor-kappa b - A pivotal transcription factor in chronic inflammatory diseases [J].
Barnes, PJ ;
Larin, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (15) :1066-1071
[5]   MURINE ENDOTHELIAL LEUKOCYTE-ADHESION MOLECULE-1 IS A CLOSE STRUCTURAL AND FUNCTIONAL HOMOLOG OF THE HUMAN PROTEIN [J].
BECKERANDRE, M ;
VANHUIJSDUIJNEN, RH ;
LOSBERGER, C ;
WHELAN, J ;
DELAMARTER, JF .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 206 (02) :401-411
[6]  
BEVILACQUA MP, 1993, ANNU REV IMMUNOL, V11, P767, DOI 10.1146/annurev.iy.11.040193.004003
[7]   ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE-1 - AN INDUCIBLE RECEPTOR FOR NEUTROPHILS RELATED TO COMPLEMENT REGULATORY PROTEINS AND LECTINS [J].
BEVILACQUA, MP ;
STENGELIN, S ;
GIMBRONE, MA ;
SEED, B .
SCIENCE, 1989, 243 (4895) :1160-1165
[8]  
CARLOS TM, 1994, BLOOD, V84, P2068
[9]   Involvement of double-stranded RNA-activated protein kinase in the synergistic activation of nuclear factor-κB by tumor necrosis factor-α and γ-interferon in preneuronal cells [J].
Cheshire, JL ;
Williams, BRG ;
Baldwin, AS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (08) :4801-4806
[10]   HUMAN P68 KINASE EXHIBITS GROWTH SUPPRESSION IN YEAST AND HOMOLOGY TO THE TRANSLATIONAL REGULATOR GCN2 [J].
CHONG, KL ;
FENG, L ;
SCHAPPERT, K ;
MEURS, E ;
DONAHUE, TF ;
FRIESEN, JD ;
HOVANESSIAN, AG ;
WILLIAMS, BRG .
EMBO JOURNAL, 1992, 11 (04) :1553-1562