Negative Feedback Between Prostaglandin and α- and β-Chemokine Synthesis in Human Microglial Cells and Astrocytes
Negative Feedback Between Prostaglandin and α- and β-Chemokine Synthesis in Human Microglial Cells and Astrocytes
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人小胶质细胞和星形胶质细胞中前列腺素与α-和β-趋化因子合成之间的负反馈
作者：
N. Janabi;I. Hau;M. Tardieu
了解脑组织中的免疫监视和炎症调节在神经免疫性疾病的治疗中是必不可少的。我们在此证明，在促炎细胞因子刺激后，原代人胶质细胞能够产生α和β趋化因子（IL-8 >生长相关蛋白α（GROα）、RANTES >微噬细胞炎性蛋白（MIP）-1α和MIP-1β），与PG（PGE 2和PGF 2 α）平行：TNF-α + IL-1β诱导所有趋化因子，但RANTES由TNF-α + IFN-γ诱导。星形胶质细胞和小胶质细胞的纯化培养物也由相同的细胞因子组合诱导，产生除了主要由星形胶质细胞产生的MIP-1α和MIP-1β之外的所有这些介质。吲哚美辛抑制PG产生导致RANTES、MIP-1α和MIP-1β增加37-60%，但GROα和IL-8分泌未增加。相比之下，使用中和抗体抑制IL-8和GRO活性会导致刺激的小胶质细胞和星形胶质细胞产生的PGE 2特异性增加6倍，但不会导致PGF 2 α的产生增加，而针对β-趋化因子的抗体则没有影响。因此，人神经胶质细胞中PG的产生下调其β-趋化因子分泌，而这些细胞中α-趋化因子的产生控制PG分泌水平。这些数据表明，在炎症条件下，PGs的实质内产生可以控制β-趋化因子的趋化梯度，以获得适当的效应细胞募集或激活。相反，脑内α-趋化因子水平升高可减少PG分泌，防止炎症和神经毒性的加重。
The understanding of immune surveillance and inflammation regulation in cerebral tissue is essential in the therapy of neuroimmunological disorders. We demonstrate here that primary human glial cells were able to produce α- and β-chemokines (IL-8 > growth related protein α (GROα) ≫ RANTES > microphage inflammatory protein (MIP)-1α and MIP-1β) in parallel to PGs (PGE2 and PGF2α) after proinflammatory cytokine stimulation: TNF-α + IL-1β induced all except RANTES, which was induced by TNF-α + IFN-γ. Purified cultures of astrocytes and microglia were also induced by the same combination of cytokines, to produce all these mediators except MIP-1α and MIP-1β, which were produced predominantly by astrocytes. The inhibition of PG production by indomethacin led to a 37–60% increase in RANTES, MIP-1α, and MIP-1β but not in GROα and IL-8 secretion. In contrast, inhibition of IL-8 and GRO activities using neutralizing Abs resulted in a specific 6-fold increase in PGE2 but not in PGF2α production by stimulated microglial cells and astrocytes, whereas Abs to β-chemokines had no effect. Thus, the production of PGs in human glial cells down-regulates their β-chemokine secretion, whereas α-chemokine production in these cells controls PG secretion level. These data suggest that under inflammatory conditions, the intraparenchymal production of PGs could control chemotactic gradient of β-chemokines for an appropriate effector cell recruitment or activation. Conversely, the elevated intracerebral α-chemokine levels could reduce PG secretion, preventing the exacerbation of inflammation and neurotoxicity.
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影响因子：
4.4
作者：
B. Rutledge;H. Rayburn;R. Rosenberg;R. North;R. Gladue;C. Corless;B. Rollins
通讯作者：
B. Rutledge;H. Rayburn;R. Rosenberg;R. North;R. Gladue;C. Corless;B. Rollins
DOI：
10.1165/ajrcmb.10.1.8292385
发表时间：
1994
影响因子：
6.4
作者：
G. M. VanOtteren;T. Standiford;S. Kunkel;J. Danforth;M. Burdick;L. Abruzzo;R. Strieter
通讯作者：
G. M. VanOtteren;T. Standiford;S. Kunkel;J. Danforth;M. Burdick;L. Abruzzo;R. Strieter
影响因子：
4.4
作者：
L. Ehrlich;Shuxian Hu;W. Sheng;Richard Sutton;G. Rockswold;Phillip K. Peterson;Chun C. Chao
通讯作者：
L. Ehrlich;Shuxian Hu;W. Sheng;Richard Sutton;G. Rockswold;Phillip K. Peterson;Chun C. Chao
关于发热发病机制的新概念。
DOI：
10.1093/clinids/10.1.168
发表时间：
1988
期刊：
Reviews of infectious diseases
影响因子：
--
作者：
Dinarello,CA;Cannon,JG;Wolff,SM
通讯作者：
Wolff,SM
影响因子：
6.4
作者：
Peterson, PK;Hu, SX;Chao, CC
通讯作者：
Chao, CC