Release of IL-1 β triggered by Milan summer PM10: molecular pathways involved in the cytokine release.
Release of IL-1 β triggered by Milan summer PM10: molecular pathways involved in the cytokine release.
复制标题
DOI：
10.1155/2013/158093
复制
发表时间：
2013
影响因子：
--
通讯作者：
Gualtieri M
中科院分区：
文献类型：
--
作者：
Bengalli R;Molteni E;Longhin E;Refsnes M;Camatini M;Gualtieri M
颗粒物（PM）暴露与肺部和心血管疾病有关，炎症状态增加。促炎性白细胞介素-（IL-）1β的释放受双重途径控制，即通过Toll样受体（TLR）活化形成无活性的pro-IL-1β，并通过NLRP 3炎性体切割。将THP-1衍生的巨噬细胞暴露于2.5 μg/cm 2的Milan PM10 6小时，并检查了通过结合TLR和激活NLRP 3促进IL-1β释放的潜力。在不存在LPS引发的情况下，夏季PM10诱导显著的IL-1β应答（与未暴露的细胞相比增加50倍），其被半胱天冬酶-1抑制剂（相对于夏季PM10处理的细胞，抑制率为91%）以及TLR-2和TLR-4抑制剂（分别为66%和53%）降低。此外，夏季PM10增加了早期内体的数量，氧化应激抑制几乎消除了PM10诱导的IL-1β反应（90%的抑制）。这些研究结果表明，夏季PM10包含的成分都涉及到激活的膜TLRs和炎症体NLPR 3的激活和TLRs的激活是至关重要的响应的幅度。ROS的形成似乎对PM10诱导的IL-1β反应很重要，但需要进一步研究以阐明介导这种作用的分子途径。
Particulate matter (PM) exposure is related to pulmonary and cardiovascular diseases, with increased inflammatory status. The release of the proinflammatory interleukin- (IL-) 1β, is controlled by a dual pathway, the formation of inactive pro-IL-1β, through Toll-like receptors (TLRs) activation, and its cleavage by NLRP3 inflammasome. THP-1-derived macrophages were exposed for 6 h to 2.5 μg/cm2 of Milan PM10, and the potential to promote IL-1β release by binding TLRs and activating NLRP3 has been examined. Summer PM10, induced a marked IL-1β response in the absence of LPS priming (50-fold increase compared to unexposed cells), which was reduced by caspase-1 inhibition (91% of inhibition respect summer PM10-treated cells) and by TLR-2 and TLR-4 inhibitors (66% and 53% of inhibition, resp.). Furthermore, summer PM10 increased the number of early endosomes, and oxidative stress inhibition nearly abolished PM10-induced IL-1β response (90% of inhibition). These findings suggest that summer PM10 contains constituents both related to the activation of membrane TLRs and activation of the inflammasome NLPR3 and that TLRs activation is of pivotal importance for the magnitude of the response. ROS formation seems important for PM10-induced IL-1β response, but further investigations are needed to elucidate the molecular pathway by which this effect is mediated.
登录
查看更多内容
影响因子：
5.6
作者：
Kovach MA;Standiford TJ
通讯作者：
Standiford TJ
影响因子：
3.2
作者：
Gualtieri, Maurizio;Ovrevik, Johan;Camatini, Marina
通讯作者：
Camatini, Marina
影响因子：
5
作者：
Franzetti, Andrea;Gandolfi, Isabella;Bestetti, Giuseppina
通讯作者：
Bestetti, Giuseppina
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
2.1
作者：
Happo, M. S.;Hirvonen, M. -R.;Salonen, R. O.
通讯作者：
Salonen, R. O.