BLOCKING THE CD38/cADPR PATHWAY PLAYS A DOUBLE-EDGED ROLE IN LPS STIMULATED MICROGLIA
BLOCKING THE CD38/cADPR PATHWAY PLAYS A DOUBLE-EDGED ROLE IN LPS STIMULATED MICROGLIA
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阻断 CD38/cADPR 通路在 LPS 刺激的小胶质细胞中发挥双刃作用
DOI：
10.1016/j.neuroscience.2017.08.010
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发表时间：
2017-10
期刊：
影响因子：
3.3
通讯作者：
Peng QY
中科院分区：
文献类型：
--
作者：
Wang Yi-Min;Liu Zhi-Yong;Ai Yu-Hang;Zhang Li-Na;Peng Qian-Yi;Zou Yu;Peng QY
CD38/环adp核糖（cADPR）通路是否在神经炎症中起保护或有害作用仍然存在争议。本研究旨在通过脂多糖（LPS）刺激的BV2小胶质细胞和共培养的神经2a （N2a）细胞来确定CD38在神经炎症中的作用。在单培养实验中，将BV2细胞分为对照组、CD38干扰组（CD38Ri）、阴性对照组（NC）、LPS组、CD38Ri + LPS组、NC + LPS组和8-Br-cADPR + LPS组。在共培养实验中，N2a细胞与BV2细胞共培养48 h， lps刺激的BV2细胞内烟酰胺腺嘌呤二核苷酸（NAD+）、cADPR、细胞内Ca2+水平和CD38表达显著升高。CD38敲除或8-Br-cADPR处理显著降低NAD+、cADPR和细胞内Ca2+水平。敲除CD38后，未处理LPS的BV2细胞iNOS和NO水平升高；然而，CD38敲除或8-Br-cADPR处理可降低LPS处理BV2细胞中的iNOS和NO水平。敲低CD38使未处理的BV2细胞中tunel阳性细胞比例和裂解Caspase 3/Caspase 3比值升高，Bcl-2/Bax比值降低；然而，CD38敲低降低了LPS处理BV2细胞的TUNEL阳性。CD38敲低或8-Br-cADPR抑制lps刺激的BV2细胞中TNF-α、IL-6和IL-1β的水平。与CD38敲除或8- br - cadpr处理的BV2细胞共培养不影响N2a细胞的凋亡或iNOS表达。总之，我们的研究结果表明，阻断CD38/cADPR通路可减少细胞内Ca2+、NO和促炎细胞因子的分泌。CD38敲低对正常小胶质细胞的凋亡和NO的产生有不利影响，而对lps刺激小胶质细胞的凋亡和NO的产生有保护作用。
Whether the CD38/cyclic ADP-ribose (cADPR) pathway plays a protective or detrimental role in neuroinflammation remains controversial. This study aimed to determine the role of CD38 in neuroinflammation using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and co-cultured Neuro-2a (N2a) cells. In monoculture experiments, BV2 cells were divided into control, CD38 interference (CD38Ri), negative control (NC), LPS, CD38Ri + LPS, NC + LPS and 8-Br-cADPR + LPS groups. In co-culture experiments, N2a cells were co-cultured with BV2 cells for 48 h. Nicotinamide adenine dinucleotide (NAD+), cADPR and intracellular Ca2+levels and CD38 expression increased significantly in LPS-stimulated BV2 cells. CD38 knockdown or 8-Br-cADPR treatment significantly reduced NAD+, cADPR and intracellular Ca2+levels. CD38 knockdown increased iNOS and NO levels in BV2 cells without LPS treatment; however, CD38 knockdown or 8-Br-cADPR treatment reduced iNOS and NO levels in BV2 cells with LPS treatment. CD38 knockdown increased the ratio of TUNEL-positive cells and cleaved Caspase 3/Caspase 3 ratio, and decreased the Bcl-2/Bax ratio in BV2 cells without LPS treatment; however, CD38 knockdown reduced the TUNEL positivity in BV2 cells with LPS treatment. CD38 knockdown or 8-Br-cADPR inhibited TNF-α, IL-6 (interleukin-6) and IL-1β levels in LPS-stimulated BV2 cells. Co-culture with CD38 knockdown or 8-Br-cADPR-treated BV2 cells did not influence apoptosis or iNOS expression in N2a cells. In conclusion, our results indicate that blocking the CD38/cADPR pathway reduces intracellular Ca2+, NO and the secretion of proinflammatory cytokines. CD38 knockdown exerted a detrimental effect in apoptosis and NO production in normal microglia, but played a protective role in apoptosis and NO production in LPS-stimulated microglia.
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影响因子：
3.7
作者：
Choe CU;Lardong K;Gelderblom M;Ludewig P;Leypoldt F;Koch-Nolte F;Gerloff C;Magnus T
通讯作者：
Magnus T
影响因子：
5.1
作者：
Hsiao, I-Lun;Chang, Chia-Cheng;Huang, Yuh-Jeen
通讯作者：
Huang, Yuh-Jeen
影响因子：
4.1
作者：
Ceni, C;Pochon, N;Moutin, MJ
通讯作者：
Moutin, MJ
影响因子：
32.4
作者：
Partida-Sánchez, S;Goodrich, S;Lund, FE
通讯作者：
Lund, FE
DOI：
--
发表时间：
2010
期刊：
--
影响因子：
--
作者：
W. Xia;Jin Han;Gang Huang;andWeihai Ying
通讯作者：
W. Xia;Jin Han;Gang Huang;andWeihai Ying