Related Experiment Videos
Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation
1Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. jhan@scripps.edu
Abstract:
For cells of the innate immune system to mount a host defence response to infection, they must recognize products of microbial pathogens such as lipopolysaccharide (LPS), the endotoxin secreted by Gram-negative bacteria. These cellular responses require intracellular signalling pathways, such as the four MAP kinase (MAPK) pathways. In mammalian cells the MAPK p38 is thought to play an important role in the regulation of cellular responses during infection through its effects on the expression of proinflammatory molecules. One means of understanding the role of p38 in these responses is to identify proteins with functions regulated by p38-catalysed phosphorylation. Here we demonstrate a link between the p38 pathway and a member of the myocyte-enhancer factor 2 (MEF2) group of transcription factors. We found that in monocytic cells, LPS increases the transactivation activity of MEF2C through p38-catalysed phosphorylation. One consequence of MEF2C activation is increased c-jun gene transcription. Our results show that p38 may influence host defence and inflammation by maintaining the balance of c-Jun protein consumed during infection.
Insights
Lipopolysaccharide (LPS) triggers innate immune cells via MAP kinase (MAPK) pathways. This study reveals p38-mediated phosphorylation activates MEF2C transcription, increasing c-jun gene expression for host defense.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Signaling
Background:
- Innate immune cells recognize microbial products like lipopolysaccharide (LPS) to initiate host defense.
- Intracellular signaling pathways, including mitogen-activated protein kinase (MAPK) pathways, are crucial for cellular responses to infection.
- The MAPK p38 is implicated in regulating cellular responses and pro-inflammatory molecule expression during infection.
Purpose of the Study:
- To investigate the role of p38 in innate immune responses.
- To identify proteins whose functions are regulated by p38-catalyzed phosphorylation.
- To elucidate the link between the p38 pathway and transcription factors involved in host defense.
Main Methods:
- Investigated the effect of LPS on monocytic cells.
- Analyzed the activation of MEF2C transcription factor.
- Examined p38-catalyzed phosphorylation of MEF2C.
- Measured c-jun gene transcription levels.
Main Results:
- Lipopolysaccharide (LPS) stimulation increases the transactivation activity of MEF2C in monocytic cells.
- MEF2C activation is mediated by p38-catalyzed phosphorylation.
- MEF2C activation leads to increased transcription of the c-jun gene.
- The p38 pathway influences c-Jun protein levels during infection.
Conclusions:
- The p38 pathway plays a significant role in regulating host defense and inflammation.
- p38-mediated phosphorylation of MEF2C is a key mechanism linking LPS recognition to inflammatory gene expression.
- This pathway contributes to maintaining the balance of c-Jun protein during infection, impacting cellular defense.