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Free Radic Biol Med:研究揭示"清除器"巨噬细胞如何在炎症过程"自保"

2017-10-22 MedSci MedSci原创

巨噬细胞(Macrophages)源自单核细胞,而单核细胞又来源于骨髓中的前体细胞。巨噬细胞和单核细胞皆为吞噬细胞,在脊椎动物体内参与非特异性防卫(先天性免疫)和特异性防卫(细胞免疫)。

巨噬细胞(Macrophages)源自单核细胞,而单核细胞又来源于骨髓中的前体细胞。巨噬细胞和单核细胞皆为吞噬细胞,在脊椎动物体内参与非特异性防卫(先天性免疫)和特异性防卫(细胞免疫)。它们的主要功能是以固定细胞或游离细胞的形式对细胞残片及病原体进行噬菌作用(即吞噬以及消化),并激活淋巴球或其他免疫细胞,令其对病原体作出反应。巨噬细胞会释出致炎物质如肿瘤坏死基因(TNF)从而活化NF-κB的基因。巨噬细胞在产生大量氧化剂的炎症过程中如何保持氧化还原稳态仍然难以捉摸。

研究人员调查了人巨噬细胞(THP1细胞)对脂多糖的炎症反应过程中,细胞内谷胱甘肽(GSH)的时间变化、主抗氧化剂、谷氨酸半胱氨酸连接酶(GCL)和GSH生物合成的限速酶的表达情况。

细胞内GSH浓度在LPS暴露早期(-6h)明显降低,后期逐渐恢复至基础水平(9-24h)。GCL催化亚基(GCLC)的表达水平与GSH的变化相似,其mRNA和蛋白水平在早期阶段降低,后期回到基础水平。相比之下,在LPS暴露阶段,GCL修饰子亚基(GCLM)的表达显著增加。在LPS暴露后3小时发生Nrf2和参与诱导GCLC和GCLM的转录因子激活,而NF-κB的活化早在30min时。研究人员用SN50抑制NF-κB信号传导阻止了GCLC的降低,抑制了LPS诱导的Nrf2活化。研究结果表明在炎症反应期间GCL和Nrf2信号传导表达的时间依赖性变化,GCLC和GCLM的调控可能通过这一过程中的不同途径。该研究为相关炎性疾病的治疗提供参考。

原始出处:
Zhang H, et al. Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages. Free Radic Biol Med. 2017 Oct 6. pii: S0891-5849(17)30791-8. doi: 10.1016/j.freeradbiomed.2017.10.010. 

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    2017-10-24 jeanqiuqiu
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    2017-12-04 sunylz
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1858803, encodeId=16ce1858803c0, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Tue Oct 24 01:44:00 CST 2017, time=2017-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767272, encodeId=1ed81e67272de, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Thu Sep 06 18:44:00 CST 2018, time=2018-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1917720, encodeId=d15b191e72036, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Dec 04 04:44:00 CST 2017, time=2017-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608137, encodeId=31f5160813eec, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Tue Oct 24 04:44:00 CST 2017, time=2017-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255397, encodeId=cfc025539ea1, content=非常好的文章.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Mon Oct 23 19:54:33 CST 2017, time=2017-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255252, encodeId=c0cf255252da, content=学习学习.继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Mon Oct 23 06:43:30 CST 2017, time=2017-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255250, encodeId=1157255250ea, content=学习学习.继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Mon Oct 23 06:41:16 CST 2017, time=2017-10-23, status=1, ipAttribution=)]
    2017-10-23 天涯183

    非常好的文章.学习了

    0

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    2017-10-23 1dd8c52fm63(暂无匿称)

    学习学习.继续关注

    0

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    2017-10-23 1dd8c52fm63(暂无匿称)

    学习学习.继续关注

    0

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