Comparisons of Cytokine Expression and Nuclear Factor-κB Activation between Respiratory Syncytial Virus Infected and Adenovirus Infected Human Bronchial Epithelial Cells

ABSTRACT Long-term macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis. Although its mechanisms remain unknown, previous studies have suggested the effects of macrolide might be anti-inflammatory rather than antibacterial. To elucidate the molecular mechanisms of its action, we studied here the effects of erythromycin (EM) and its new derivative, EM703, which shows no antibacterial action, on the activation of the transcription factor nuclear factor-κB (NF-κB) in human bronchial epithelial cells. Western blotting analysis showed that EM did not inhibit the degradation of IκBα, suggesting the molecular target for EM was not the dissociation of NF-κB from IκB. An electrophoretic mobility shift assay showed that EM did not interrupt the NF-κB DNA-binding activity in the nucleus under the conditions tested. Moreover, not only EM but also EM703 suppressed the activation of NF-κB and the production of interleukin-8, demonstrating that the anti-inflammatory action of the macrolide is independent of its antibacterial activity. Taken together, these data suggest EM has an anti-inflammatory action, presumably via an interaction with the NF-κB signaling pathway in the downstream of the dissociation from IκB, resulting in the inhibition of NF-κB.

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Protein Kinase C-α Activity Is Required for Respiratory Syncytial Virus Fusion to Human Bronchial Epithelial Cells

Journal of Virology ◽

10.1128/jvi.78.24.13717-13726.2004 ◽

2004 ◽

Vol 78 (24) ◽

pp. 13717-13726 ◽

Cited By ~ 14

Author(s):

Homero San-Juan-Vergara ◽

Mark E. Peeples ◽

Richard F. Lockey ◽

Shyam S. Mohapatra

Keyword(s):

Protein Kinase C ◽

Respiratory Syncytial Virus ◽

Protein Kinase ◽

Epithelial Cells ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Kinase C ◽

Rsv Infection ◽

Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) infection activates protein kinase C (PKC), but the precise PKC isoform(s) involved and its role(s) remain to be elucidated. On the basis of the activation kinetics of different signaling pathways and the effect of various PKC inhibitors, it was reasoned that PKC activation is important in the early stages of RSV infection, especially RSV fusion and/or replication. Herein, the role of PKC-α during the early stages of RSV infection in normal human bronchial epithelial cells is determined. The results show that the blocking of PKC-α activation by classical inhibitors, pseudosubstrate peptides, or the overexpression of dominant-negative mutants of PKC-α in these cells leads to significantly decreased RSV infection. RSV induces phosphorylation, activation, and cytoplasm-to-membrane translocation of PKC-α. Also, PKC-α colocalizes with virus particles and is required for RSV fusion to the cell membrane. Thus, PKC-α could provide a new pharmacological target for controlling RSV infection.

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