J Hepatol：肝细胞特异性缺失的IL1-RI，通过阻断IL-1驱动的自体炎症，减轻了肝脏损伤

2018-04-21 MedSci MedSci原创

肝细胞中的IL-1R1通过IL-1驱动的细胞死亡和炎症反应，发挥关键作用

研究背景和目的：白细胞介素(IL)-1型细胞因子包括IL-1α、IL-β和白细胞介素-1受体拮抗剂(IL- 1Ra)，它们是先天免疫系统中最有效的分子，通过泛素表达的白细胞介素-1受体1 (IL-1R1)发挥生物活性。肝细胞中的IL-1R1在急性肝衰竭(ALF)中的作用仍未确定。

研究方法：本研究采用了一种新的转基因小鼠模型，去除了肝细胞内具有信号传导能力的所有IL-1R亚型(Il1r1(Hep-/-))，去研究研究IL-1R1在ALF中的作用。

研究结果：由D-galactosamine (D-GalN)和脂多糖(LPS)诱导的ALF，在Il1r1(Hep-/-)小鼠中发生的频率显著降低，死亡率降低。条件性去除Il1r1，损伤了c-Jun n -末端激酶(JNK)/c-Jun信号的激活；激活了核因子-kappaB (NF-kappaB) p65；抑制细胞外信号调节激酶(ERK)；阻止了caspase 3介导的细胞凋亡。此外，Il1r1(Hep-/-)小鼠表现出局部和全身炎症细胞因子和趋化因子水平的降低，特别是TNF-α、IL-α/β、IL-6、CC-趋化因子配体2 (CCL2)、C-X-C motif配体1(CXCL-1)和CXCL-2，以及减少中性粒细胞招募进入肝组织以应对损伤。在肝细胞缺乏IL-1R1的情况下，NLRP3炎性体表达和caspase 1活化被抑制。使用IL-1ra (anakinra)抑制IL-1R1，降低了肝脏损伤的严重程度；然而补充IL-1alpha后，肝脏损伤程度加大。这些效应在体内和后期都失去了作用，支持IL-1R1在急性肝损伤中扮演炎性信号放大的作用。

研究结论：肝细胞中的IL-1R1通过IL-1驱动的细胞死亡和炎症反应，发挥关键作用。

原始出处：

Gehrke N， Hovelmeyer N， Waisman A， et al. Hepatocyte-specific deletion of IL1-RI attenuates liver injury by blocking IL-1 driven autoinflammation.J Hepatol， 2018， 68(5)， 986-995. doi： 10.1016/j.jhep.2018.01.008.

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2018-10-05 Boyinsh

#肝脏损伤#

44 0
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2018-10-20 wgsun

#细胞特异性#

44 0
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2018-08-23 jinweidong

#特异性#

38 0
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2018-07-01 xjy02

#肝细胞#

39 0
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2018-04-24 41514497@qq.com

#阻断#

34 0
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2018-04-23 ms3046638856685384

#损伤#

33 0
[GetPortalCommentsPageByObjectIdResponse(id=1743306, encodeId=2aa41e433062a, content=<a href='/topic/show?id=e87881445de' target=_blank style='color:#2F92EE;'>#肝脏损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81445, encryptionId=e87881445de, topicName=肝脏损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=315735073803, createdName=Boyinsh, createdTime=Fri Oct 05 03:09:00 CST 2018, time=2018-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993742, encodeId=404a1993e428f, content=<a href='/topic/show?id=f7c4e79590d' target=_blank style='color:#2F92EE;'>#细胞特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77959, encryptionId=f7c4e79590d, topicName=细胞特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Sat Oct 20 14:09:00 CST 2018, time=2018-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899211, encodeId=a9e1189921166, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Thu Aug 23 21:09:00 CST 2018, time=2018-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863359, encodeId=7b1d186335903, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Sun Jul 01 06:09:00 CST 2018, time=2018-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710132, encodeId=14fd1e10132a4, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Tue Apr 24 23:09:00 CST 2018, time=2018-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397519, encodeId=96a8139e519d4, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Mon Apr 23 06:09:00 CST 2018, time=2018-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427090, encodeId=1c4a142e090da, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Mon Apr 23 06:09:00 CST 2018, time=2018-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508213, encodeId=0beb150821396, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Mon Apr 23 06:09:00 CST 2018, time=2018-04-23, status=1, ipAttribution=)]
2018-04-23 gwc384

#EPA#

24 0
[GetPortalCommentsPageByObjectIdResponse(id=1743306, encodeId=2aa41e433062a, content=<a href='/topic/show?id=e87881445de' target=_blank style='color:#2F92EE;'>#肝脏损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81445, encryptionId=e87881445de, topicName=肝脏损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=315735073803, createdName=Boyinsh, createdTime=Fri Oct 05 03:09:00 CST 2018, time=2018-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993742, encodeId=404a1993e428f, content=<a href='/topic/show?id=f7c4e79590d' target=_blank style='color:#2F92EE;'>#细胞特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77959, encryptionId=f7c4e79590d, topicName=细胞特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Sat Oct 20 14:09:00 CST 2018, time=2018-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899211, encodeId=a9e1189921166, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Thu Aug 23 21:09:00 CST 2018, time=2018-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1863359, encodeId=7b1d186335903, content=<a href='/topic/show?id=c0b68135561' target=_blank style='color:#2F92EE;'>#肝细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81355, encryptionId=c0b68135561, topicName=肝细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Sun Jul 01 06:09:00 CST 2018, time=2018-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710132, encodeId=14fd1e10132a4, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Tue Apr 24 23:09:00 CST 2018, time=2018-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397519, encodeId=96a8139e519d4, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Mon Apr 23 06:09:00 CST 2018, time=2018-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427090, encodeId=1c4a142e090da, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Mon Apr 23 06:09:00 CST 2018, time=2018-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508213, encodeId=0beb150821396, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Mon Apr 23 06:09:00 CST 2018, time=2018-04-23, status=1, ipAttribution=)]
2018-04-23 jjjiang0202

#IL-1#

21 0

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肝病

J Hepatol：肝细胞特异性缺失的IL1-RI，通过阻断IL-1驱动的自体炎症，减轻了肝脏损伤

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