Integrin CD11b attenuates DSS-induced colitis by promoting TLR-triggered IL-10 expression in macrophages via Src/Akt pathway
Integrin CD11b attenuates DSS-induced colitis by promoting TLR-triggered IL-10 expression in macrophages via Src/Akt pathway
复制标题
整合素 CD11b 通过 Src/Akt 途径促进巨噬细胞中 TLR 触发的 IL-10 表达，从而减轻 DSS 诱导的结肠炎
DOI：
10.1016/j.cyto.2014.07.074
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发表时间：
2016
影响因子：
4.6
通讯作者：
Cao Xuetao
中科院分区：
文献类型：
--
作者：
Hu Xiang;Han Chaofeng;Li Nan;Cao Xuetao
过敏性皮肤炎症，如特应性皮炎（AD），其特征是水肿和浸润各种炎症细胞，如肥大细胞、T细胞和巨噬细胞。巨噬细胞在炎症发生、增殖和消退过程中起着重要的作用。白细胞介素-6 （IL-6）是受刺激的巨噬细胞中产生的具有代表性的促炎细胞因子，可诱导有害的炎症状态。本研究旨在探讨DPHC在RAW 264.7小鼠巨噬细胞和AD小鼠模型中的抗炎作用及其作用机制。DPHC以剂量依赖的方式抑制LPS诱导的IL-6的产生，并抑制LPS诱导炎症过程中的中心信号分子NF-κ B的磷酸化或核易位。此外，已知的NF-κ B抑制剂（pyrolidine dithiocarbamate， PDTC， n - toyl - l苯丙氨酸氯甲基酮，TPCK, Parthenolide）强烈抑制IL-6的产生。然而，DPHC对丝裂原激活的蛋白激酶途径（JNK、ERK和P-38）和LPS激活的STAT1、3和5途径没有或只有很小的影响。在AD小鼠模型中，dphc处理组与诱导组相比，免疫球蛋白E （IgE）、耳部厚度和炎症细胞浸润明显降低。此外，与诱导组相比，DPHC治疗导致淋巴结大小更小，厚度和长度减少。这些结果提示DPHC可能有效治疗AD的过敏症状。本研究由韩国政府国家研究基金（MEST）资助（NRF-C1ABA001-2011-0021039）。
Allergic skin inflammation such as atopic dermatitis (AD) is characterized by edema and infiltration with various inflammatory cells such as mast cells, T cells and macrophages. Macrophages are important player that involved inflammation process including initiation, propagation, and resolution. Interleukin-6 (IL-6) is a representative pro-inflammatory cytokine generated in stimulated macrophage and induces deleterious inflammatory states. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in the RAW 264.7 murine macrophages and AD mice model. DPHC inhibit LPS-induced IL-6 production in a dose dependent manner and suppressed the phosphorylation or the nuclear translocation of NF-κ B, a central signaling molecule in LPS induced inflammation process. Furthermore, the known inhibitors of NF-κ B (pyrrolidine dithiocarbamate; PDTC, N-tosyl-Lphenylalanine chloromethyl ketone; TPCK, Parthenolide) strongly inhibited IL-6 production. However, DPHC had no or only minimal effects on the mitogen activated protein kinase pathways (JNK, ERK and P-38) and STAT1, 3, and 5 pathways activated by LPS. In AD mice model, the DPHC-treated group showed significantly decreased immunoglobulin E (IgE), ear thickness and inflammatory cell infiltration compared with the induction group. In addition, DPHC treatment resulted in a smaller lymph node size with reduced the thickness and length compared to the induction group. These results suggest that DPHC may be effective in treating the allergic symptoms of AD. This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST)(NRF-C1ABA001-2011-0021039).