Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
PLoS One. 2012;7(1):e31049. doi: 10.1371/journal.pone.0031049. Epub 2012 Jan 27.
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.
富含 CARD 的 MAGUK 蛋白 1（CARMA1）在 T 细胞的 T 细胞受体（TCR）激活后调节适应性免疫反应中发挥着关键作用。其在调节宿主黏膜固有免疫反应（如粘蛋白的上调）中的作用尚不清楚。在这里，我们发现 CARMA1 作为一种关键的信号转导介质，可协同上调呼吸道上皮细胞中细菌不可分型流感嗜血杆菌（NTHi）和佛波酯 PMA 对 MUC5AC 粘蛋白的表达。NTHi 诱导的 TLR 依赖性 TRAF6-MKK3-p38 MAPK 信号通路与 PKCθ-MEK-ERK 信号通路协同作用。CARMA1 通过 TRAF6 在此协同作用中发挥关键作用，从而导致 MUC5AC 粘蛋白的协同上调。因此，我们的研究揭示了 CARMA1 在介导宿主黏膜固有免疫反应中的新作用。
