PKCθ synergizes with TLR-dependent TRAF6 signaling pathway to upregulate MUC5AC mucin via CARMA1

PLoS One. 2012;7(1):e31049. doi: 10.1371/journal.pone.0031049. Epub 2012 Jan 27.

Abstract

CARD-containing MAGUK protein 1 (CARMA1) plays a crucial role in regulating adaptive immune responses upon T-cell receptor (TCR) activation in T cells. Its role in regulating host mucosal innate immune response such as upregulation of mucin remains unknown. Here we show that CARMA1 acts as a key signaling mediator for synergistic upregulation of MUC5AC mucin by bacterium nontypeable Haemophilus influenzae (NTHi) and phorbol ester PMA in respiratory epithelial cells. NTHi-induced TLR-dependent TRAF6-MKK3-p38 MAPK signaling pathway synergizes with PKCθ-MEK-ERK signaling pathway. CARMA1 plays a crucial role in mediating this synergistic effect via TRAF6, thereby resulting in synergistic upregulation of MUC5AC mucin. Thus our study unveils a novel role for CARMA1 in mediating host mucosal innate immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins / metabolism*
  • Cell Line
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology
  • Epithelial Cells / microbiology
  • Guanylate Cyclase / metabolism*
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / physiology
  • Humans
  • Isoenzymes / metabolism*
  • MAP Kinase Kinase 3 / metabolism
  • MAP Kinase Kinase 6 / metabolism
  • MAP Kinase Signaling System / drug effects
  • Membrane Proteins / metabolism*
  • Mice
  • Mucin 5AC / metabolism*
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Signal Transduction* / drug effects
  • TNF Receptor-Associated Factor 6 / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Toll-Like Receptor 2 / metabolism*
  • Up-Regulation* / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • CARD Signaling Adaptor Proteins
  • Isoenzymes
  • Membrane Proteins
  • Mucin 5AC
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 2
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 3
  • MAP Kinase Kinase 6
  • CARD11 protein, human
  • Guanylate Cyclase
  • Tetradecanoylphorbol Acetate