Mitogen-activated protein kinase phosphatase-1 and septic shock

Yusen Liu*, Thomas P. Shanley

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Mitogen-activated protein (MAP) kinase cascades are crucial signal transduction pathways in the biosynthesis of pro-inflammatory cytokines. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, plays a pivotal role in the feedback control of p38 and c-Jun N-terminal kinase (JNK). In vitro studies using cultured macrophages have provided strong evidence for a critical role of MKP-1 in the restraint of pro-inflammatory cytokine biosynthesis. Recently, a number of studies conducted using MKP-1 knockout mice have verified the importance of MKP-1 in the regulation of p38 and JNK and also in the regulation of pro-inflammatory cytokine synthesis. Upon lipopolysaccharide challenge, MKP-1 knockout mice produced dramatically greater amounts of inflammatory cytokines, developed severe hypotension, and multi-organ failure, and exhibited a remarkable increase in mortality. These studies demonstrate that MKP-1 is an essential feedback regulator of the innate immune response, and that it plays a critical role in preventing septic shock and multi-organ dysfunction during pathogenic infection.

Original languageEnglish (US)
Pages (from-to)66-78
Number of pages13
JournalJournal of Organ Dysfunction
Volume5
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Cytokine
  • Feedback
  • Inflammation
  • Innate immunity
  • Kinase/phosphatase
  • Macrophages
  • Sepsis
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Critical Care
  • Critical Care and Intensive Care Medicine

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