Activation of Erk2 by Respiratory Syncytial Virus in A549 Cells Is Linked to the Production of Interleukin 8

Abstract

The airway inflammation that results from respiratory syncytial virus infection is associated with a marked increase in interleukin 8 and neutrophils in the infected sites of the lung. In this study, the relationship between production of interleukin 8, infection of A549 cells by the virus, and activation of mitogen-activated protein kinases (MAPKs) was investigated. Infection of A549 cells by the virus caused an increase on the activity of extracellular signal-regulated kinase 2 (ERK2) by about 10-fold compared with the noninfected cells. The increase in the activity of ERK2 during the viral infection was an immediate event and occurred prior to the viral replication process. PD98059, which blocks the activation of MAPK/ERK kinase 1 (MEK1), inhibited the increase in the activity of ERK2 by infection of respiratory syncytial virus by about 50% at 10 microM. Pretreatment of A549 cells with PD98059 before the viral infection also inhibited the increase in the production of interleukin 8 by 50%, but had little effect on the mRNA level. The viral infection had no effect on the activities of p38 and c-jun N-terminal kinase (JNK). These observations suggest that activation of ERK2 by respiratory syncytial virus infection may be one of the mechanisms that result in the increase of the production of interleukin 8.

Activation of the Epidermal Growth Factor Receptor by Respiratory Syncytial Virus Results in Increased Inflammation and Delayed Apoptosis

“…The three major MAP kinase families are the ERK (1,2, 5, 7, and 8), p38 (␣, ␤, ␥, and ␦) and c-Jun N-terminal kinase (1, 2, and 3) (32,33). We have found a requirement for ERK activation in RSV-induced IL-8 production (8). More recently we have shown that ERK activation plays an important role in prolonged survival of RSV-infected airway epithelial cells (10).…”

Respiratory Syncytial Virus Infection of Human Lung Endothelial Cells Enhances Selectively Intercellular Adhesion Molecule-1 Expression

“…Three major types of MAPK cascades have been reported in mammalian cells, namely the ERK1/ERK2 cascade, the JNK/stress-activated protein kinase cascade, and the p38 kinase pathway. The activity of the MEK, ERK and p38 kinase in RSV-infected epithelial cells has been linked to RSV replication, IL-8 release, and posttranscriptional RANTES gene expression, respectively (35,46,47). Moreover, it was reported that expression of TNF-␣ and IL-1␤ in RSV-infected epithelial cells required the activation of the p38 MAPK pathway (48).…”

Induction of IL-8 Release in Lung Cells via Activator Protein-1 by Recombinant Baculovirus Displaying Severe Acute Respiratory Syndrome-Coronavirus Spike Proteins: Identification of Two Functional Regions

“…For example, both adenovirus type 7 and respiratory syncytial virus induced IL-8 production through the activation of ERK in A549 cells (22,23), and the rhinovirus or TNF-␣ induced IL-8 production through the activation of p38 in BEAS-2B or rheumatoid fibroblast cells (24,25). IL-1 induced IL-8 production through the activation of JNK in KB epithelial cells (26).…”

“…The transcriptional activity of AP-1 has been reported to be regulated by MAPKs (22)(23)(24)(25)(26)(27). Therefore, vAtEpGS688-induced MAPK activation was examined.…”