衰老小鼠巨噬细胞中促 IL-1β 反应缺陷。
Defective pro-IL-1β responses in macrophages from aged mice.
机构信息
Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, S6-862, 55 Lake Avenue North, Worcester, MA, 01655, USA.
出版信息
Immun Ageing. 2012 Dec 11;9(1):27. doi: 10.1186/1742-4933-9-27.
BACKGROUND
Cytokines regulated by the inflammasome pathway have been extensively implicated in various age-related immune pathologies. We set out to elucidate the contribution of the nod-like receptor protein 3 (NLRP3) inflammasome pathway to the previously described deficiencies in IL-1β production by macrophages from aged mice. We examined the production of pro-IL-1β and its conversion into IL-1β as two separate steps and compared these cytokine responses in bone marrow derived macrophages from young (6-8 weeks) and aged (18-24 months) C57BL/6 mice.
FINDINGS
Relative to macrophages from young mice, macrophages from aged mice produced less pro-IL-1β after TLR4 stimulation with LPS. However upon activation of the NLRP3 inflammasome with ATP, macrophages from young and aged mice were able to efficiently convert and secrete intracellular pro-cytokines as functional cytokines.
CONCLUSIONS
Lower levels of IL-1β production are a result of slower and lower overall production of pro-IL-1β in macrophages from aged mice.
背景
炎性小体途径调控的细胞因子广泛参与各种与年龄相关的免疫病理学。我们旨在阐明 NOD 样受体蛋白 3（NLRP3）炎性小体途径对先前描述的老年小鼠巨噬细胞中 IL-1β 产生缺陷的贡献。我们检测了前体白细胞介素 1β（pro-IL-1β）的产生及其转化为白细胞介素 1β（IL-1β）作为两个独立的步骤，并比较了来自年轻（6-8 周）和老年（18-24 个月）C57BL/6 小鼠骨髓来源巨噬细胞的细胞因子反应。
结果
与年轻小鼠的巨噬细胞相比，LPS 刺激 TLR4 后，老年小鼠的巨噬细胞产生的前体白细胞介素 1β 较少。然而，在用 ATP 激活 NLRP3 炎性小体后，来自年轻和老年小鼠的巨噬细胞能够有效地将细胞内前细胞因子转化并分泌为功能性细胞因子。
结论
老年小鼠巨噬细胞中 IL-1β 产生水平较低是由于前体白细胞介素 1β 的产生速度较慢且总体水平较低所致。
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