Journal article
Respiratory Syncytial Virus Infection Results in Activation of Multiple Protein Kinase C Isoforms Leading to Activation of Mitogen-Activated Protein Kinase
The Journal of immunology (1950), Vol.166(4), pp.2681-2687
02/15/2001
DOI: 10.4049/jimmunol.166.4.2681
PMID: 11160332
Abstract
Respiratory syncytial virus (RSV) is an important respiratory pathogen that preferentially infects epithelial cells in the airway and causes a local inflammatory response. Very little is known about the second messenger pathways involved in this response. To characterize some of the acute response pathways involved in RSV infection, we used cultured human epithelial cells (A549) and optimal tissue culture-infective doses (TCID(50)) of RSV. We have previously shown that RSV-induced IL-8 release is linked to activation of the extracellular signal-related kinase (ERK) mitogen-activated protein kinase pathway. In this study, we evaluated the upstream events involved in ERK activation by RSV. RSV activated ERK at two time points, an early time point consistent with viral binding and a later sustained activation consistent with viral replication. We next evaluated the role of protein kinase C (PKC) isoforms in RSV-induced ERK kinase activity. We found that A549 cells contain the Ca(2+)-dependent isoforms alpha and beta1, and the Ca(2+)-independent isoforms delta, epsilon, eta, mu, theta, and zeta. Western analysis showed that RSV caused no change in the amounts of these isoforms. However, kinase activity assays demonstrated activation of isoform zeta within 10 min of infection, followed by a sustained activation of isoforms beta1, delta, epsilon, and mu 24-48 h postinfection. A cell-permeable peptide inhibitor specific for the zeta isoform decreased early ERK kinase activation by RSV. Down-regulation of the other PKC isoforms with PMA blocked the late sustained activation of ERK by RSV. These studies suggest that RSV activates multiple PKC isoforms with subsequent downstream activation of ERK kinase.
Details
- Title: Subtitle
- Respiratory Syncytial Virus Infection Results in Activation of Multiple Protein Kinase C Isoforms Leading to Activation of Mitogen-Activated Protein Kinase
- Creators
- Martha M MonickJanice M StaberKarl W ThomasGary W Hunninghake
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.166(4), pp.2681-2687
- DOI
- 10.4049/jimmunol.166.4.2681
- PMID
- 11160332
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 02/15/2001
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Hematology/Oncology; Internal Medicine
- Record Identifier
- 9984070955702771
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