PKCθ synergizes with TLR-dependent TRAF6 signaling pathway to upregulate MUC5AC mucin via CARMA1.
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.
Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
Hirofumi
H
Jono
Jae Hyang
JH
Lim
Haidong
H
Xu
Jian-Dong
JD
Li
D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006193:Haemophilus influenzae / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D048371:MAP Kinase Kinase 3 / Q000378:metabolism; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D055271:Mucin 5AC / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D015398:Signal Transduction / Q000187:drug effects; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D053468:CARD Signaling Adaptor Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D055271:Mucin 5AC; D048029:TNF Receptor-Associated Factor 6; D051195:Toll-Like Receptor 2; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; C426242:CARD11 protein, human; D006162:Guanylate Cyclase; D013755:Tetradecanoylphorbol Acetate