Leptin induces interleukin‐1β release from rat microglial cells through a caspase 1 independent mechanism
Leptin induces interleukin‐1β release from rat microglial cells through a caspase 1 independent mechanism
复制标题
瘦素通过 caspase 1 独立机制诱导大鼠小胶质细胞释放白介素-1β
DOI：
10.1111/j.1471-4159.2007.04559.x
复制
发表时间：
2007
影响因子：
4.7
通讯作者：
G. Luheshi
中科院分区：
文献类型：
--
作者：
E. Pinteaux;W. Inoue;Lorraine Schmidt;F. Molina;N. Rothwell;G. Luheshi
瘦素通过抑制食欲和增加下丘脑的能量消耗来调节能量平衡。最近，我们证明瘦素的作用至少部分是由大脑中白细胞介素(IL) - 1β的释放介导的。小胶质细胞是大脑中IL - 1β的主要来源，但尚不清楚这些细胞是否表达瘦素受体，或对瘦素作出反应以产生IL - 1β。利用RT - PCR和免疫细胞化学，我们证明了大鼠小胶质细胞表达瘦素受体（Ob - R）s的短（非信号传导）和长（信号传导）亚型。在瘦素处理（0.01-10 μg/mL） 24小时后收集的细胞培养基上进行的免疫分析显示，IL - 1β及其内源性受体拮抗剂IL - 1RA的产生和释放呈剂量依赖性。此外，瘦素诱导的IL - 1β释放通过信号换能器和转录激活因子3 （STAT3）依赖机制发生。Western blot分析表明，瘦素诱导小胶质细胞合成pro - IL - 1β，并在培养基中释放成熟的17 kDa亚型。瘦素诱导的IL - 1β释放既不受caspase抑制剂BOC‐D‐FMK的抑制，也不受caspase抑制剂Ac‐YVAD‐CHO的抑制，这表明IL - 1的裂解与caspase活性无关。这些结果证实了我们早期在体内的观察结果，并证明小胶质细胞是大脑中对瘦素作出反应的IL - 1β的重要来源。
Leptin regulates energy balance by suppressing appetite and increasing energy expenditure through actions in the hypothalamus. Recently we demonstrated that the effects of leptin are, at least in part, mediated by the release of interleukin (IL)‐1β in the brain. Microglia constitute the major source of IL‐1β in the brain but it is not known whether these cells express leptin receptors, or respond to leptin to produce IL‐1β. Using RT‐PCR and immunocytochemistry, we demonstrate that primary rat microglial cells express the short (non‐signalling) and long (signalling) isoforms of the leptin receptors (Ob‐R)s. Immunoassays performed on cell medium collected 24 h after leptin treatment (0.01–10 μg/mL) demonstrated a dose‐dependent production and release of IL‐1β and its endogenously occurring receptor antagonist IL‐1RA. In addition leptin‐induced IL‐1β release occurs via a signal transducer and activator of transcription 3 (STAT3)‐dependent mechanism. Western blot analysis demonstrated that leptin induced the synthesis of pro‐IL‐1β in microglial cells and the release of mature 17 kDa isoform into the culture medium. Leptin‐induced IL‐1β release was neither inhibited by the pan‐caspase inhibitor BOC‐D‐FMK, nor by the caspase 1 inhibitor Ac‐YVAD‐CHO indicating that IL‐1 cleavage is independent of caspase activity. These results confirm our earlier observations in vivo and demonstrate that microglia are an important source of IL‐1β in the brain in response to leptin.
登录
查看更多内容
从肿瘤细胞系 U937 中纯化和表征独特的人白细胞介素 1。
DOI：
--
发表时间：
1986
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Knudsen,PJ;Dinarello,CA;Strom,TB
通讯作者：
Strom,TB
DOI：
10.1073/pnas.93.25.14564
发表时间：
1996-12-10
影响因子：
11.1
作者：
Gainsford, T;Willson, TA;Hilton, DJ
通讯作者：
Hilton, DJ
DOI：
10.1152/ajpcell.1999.276.2.c386
发表时间：
1999-02-01
影响因子：
5.5
作者：
Lee, FYJ;Li, YB;Diehl, AM
通讯作者：
Diehl, AM
影响因子：
15.9
作者：
Gabay, C;Smith, MF;Arend, WP
通讯作者：
Arend, WP
瘦素和糖皮质激素对下丘脑 IL-1β 基因表达的生理调节：对能量稳态的影响。
DOI：
10.1152/ajpendo.00038.2004
发表时间：
2004
期刊：
American journal of physiology. Endocrinology and metabolism.
影响因子：
--
作者：
Wisse,BrentE;Ogimoto,Kayoko;Morton,GregoryJ;Wilkinson,CharlesW;Frayo,RScott;Cummings,DavidE;Schwartz,MichaelW
通讯作者：
Schwartz,MichaelW