Double-Stranded RNA-Activated Protein Kinase Regulates Early Innate Immune Responses During Respiratory Syncytial Virus Infection

被引：9

作者：

Minor, Radiah A. Corn ^{[3
]}

Limmon, Gino V. ^{[4
]}

Miller-DeGraff, Laura ^{[1
]}

Dixon, Darlene ^{[1
]}

Andrews, Danica M. K. ^{[1
]}

Kaufman, Randal J. ^{[2
]}

Imani, Farhad ^{[1
]}

机构：

[1] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA

[2] Univ Michigan, Dept Biochem, Ann Arbor, MI 48109 USA

[3] N Carolina A&T Univ, Greensboro, NC USA

[4] Ctr Life Sci, Singapore MIT Alliance Res & Technol, Singapore, Singapore

来源：

JOURNAL OF INTERFERON AND CYTOKINE RESEARCH | 2010年 / 30卷 / 04期

关键词：

NF-KAPPA-B; AIRWAY EPITHELIAL-CELLS; TNF-ALPHA; IN-VITRO; NASOPHARYNGEAL SECRETIONS; MAPK ACTIVATION; MESSENGER-RNA; PKR; INTERFERON; MICE;

D O I：

10.1089/jir.2009.0051

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：

Respiratory syncytial virus (RSV) is the most common cause of childhood viral bronchiolitis and lung injury. Inflammatory responses significantly contribute to lung pathologies during RSV infections and bronchiolitis but the exact mechanisms have not been completely defined. The double-stranded RNA-activated protein kinase (PKR) functions to inhibit viral replication and participates in several signaling pathways associated with innate inflammatory immune responses. Using a functionally defective PKR (PKR-/-) mouse model, we investigated the role of this kinase in early events of RSV-induced inflammation. Our data showed that bronchoalveolar lavage (BAL) fluid from infected PKR-/- mice had significantly lower levels of several innate inflammatory cytokines and chemokines. Histological examinations revealed that there was less lung injury in infected PKR-/- mice as compared to the wild type. A genome-wide analysis showed that several early antiviral and immune regulatory genes were affected by PKR activation. These data suggest that PKR is a signaling molecule for immune responses during RSV infections.

引用

页码：263 / 272

页数：10

共 65 条

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