MAPK activation is involved in posttranscriptional regulation of RSV-induced RANTES gene expression

Konrad Pazdrak, Barbara Olszewska-Pazdrak, Tianshuang Liu, Ryuta Takizawa, Allan R. Brasier, Roberto P. Garofalo, Antonella Casola

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Airway epithelial cells represent the primary cell target of respiratory syncytial virus (RSV) infection. They actively participate in the lung immune/inflammatory response that follows RSV infection by expressing chemokines, small chemotactic cytokines that recruit and activate leukocytes. Regulated on activation, normal T cell expressed, and presumably secreted (RANTES) is a member of the CC chemokine subfamily and is strongly chemotactic for T lymphocytes, monocytes, basophils, and eosinophils, cell types that are present or activated in the inflammatory infiltrate that follows RSV infection of the lung. RSV infection of airway epithelial cells induces RANTES expression by increasing gene transcription and stabilizing RNA transcripts. The signaling pathway regulating RANTES gene expression after RSV infection has not been determined. In this study, we examined the role of extracellular signal-regulated kinase (ERK) and p38, members of the mitogen-activated protein (MAP) kinase (MAPK) family, in RSV-induced RANTES production. RSV infection of alveolar epithelial cells induced increased phosphorylation and catalytic activity of ERK and the upstream kinases Raf-1 and MAP ERK kinase. Induction of the MAP signaling cascade required a replication-competent virus. RSV infection of alveolar epithelial cells also induced activation of p38 MAPK. Inhibition of ERK and p38 activation significantly reduced RSV-induced RANTES mRNA and protein secretion without affecting RANTES gene transcription or transcription factor activation. These results indicate that the MAPK signaling cascade regulates RANTES production in alveolar epithelial cells through a posttranscriptional mechanism.

Original languageEnglish (US)
Pages (from-to)L364-L372
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number2 27-2
DOIs
StatePublished - Jan 1 2002

Keywords

  • Chemokine
  • Gene regulation
  • Mitogen-activated protein kinase
  • Normal T cell expressed
  • Presumably secreted
  • Regulated on activation
  • Respiratory syncytial virus
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'MAPK activation is involved in posttranscriptional regulation of RSV-induced RANTES gene expression'. Together they form a unique fingerprint.

  • Cite this