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

Hirofumi Jono, Jae Hyang Lim, Haidong Xu, Jian Dong Li

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Article numbere31049
JournalPLoS ONE
Volume7
Issue number1
DOIs
StatePublished - 27 Jan 2012

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