| First Author | Bandyopadhyay SK | Year | 2000 |
| Journal | J Immunol | Volume | 164 |
| Issue | 4 | Pages | 2077-83 |
| PubMed ID | 10657661 | Mgi Jnum | J:60332 |
| Mgi Id | MGI:1353178 | Doi | 10.4049/jimmunol.164.4.2077 |
| Citation | Bandyopadhyay SK, et al. (2000) Induction of E-selectin expression by double-stranded RNA and TNF-alpha is attenuated in murine aortic endothelial cells derived from double-stranded RNA-activated kinase (PKR)-null mice. J Immunol 164(4):2077-83 |
| abstractText | 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-kappaB, 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-kappaB 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-kappaB-dependent pathway. In PKR-null cells, pIC-mediated degradation of IkappaBbeta is deficient. Activation of this pathway requires the PKR-dependent degradation of the IkappaBbeta 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. |
