Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release.
Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release.
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DOI：
10.1084/jem.20120189
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发表时间：
2012-08-27
期刊：
影响因子：
--
通讯作者：
Bianchi ME
中科院分区：
文献类型：
--
作者：
Venereau E;Casalgrandi M;Schiraldi M;Antoine DJ;Cattaneo A;De Marchis F;Liu J;Antonelli A;Preti A;Raeli L;Shams SS;Yang H;Varani L;Andersson U;Tracey KJ;Bachi A;Uguccioni M;Bianchi ME
HMGB1通过在互斥氧化还原状态之间切换，协调白细胞募集和诱导炎性细胞因子的分泌。组织损伤引起炎症，通过招募白细胞并激活它们释放促炎介质。我们发现高迁移率的组框1蛋白（HMGB1）通过在互斥的氧化还原状态之间切换来协调这两个过程。半胱氨酸的减少使HMGB1成为化学引诱剂，而二硫键使其成为促炎细胞因子，而半胱氨酸进一步被活性氧氧化为磺酸盐则消除了这两种活性。我们发现白细胞的募集和激活是可以分离的。一种不可氧化的HMGB1突变体，其中丝氨酸取代所有半胱氨酸（3S-HMGB1）不促进细胞因子的产生，但在体内招募白细胞方面比野生型HMGB1更有效。HMGB1抑制剂BoxA干扰白细胞募集，但不干扰活化。我们在受伤肌肉中检测了HMGB1的不同氧化还原形式。HMGB1首先被完全还原，随后形成二硫键。因此，HMGB1通过采用互斥的氧化还原状态，协调无菌炎症、白细胞募集及其诱导炎症细胞因子分泌的关键事件。
HMGB1 orchestrates leukocyte recruitment and their induction to secrete inflammatory cytokines by switching between mutually exclusive redox states. Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to sulfonates by reactive oxygen species abrogates both activities. We show that leukocyte recruitment and activation can be separated. A nonoxidizable HMGB1 mutant in which serines replace all cysteines (3S-HMGB1) does not promote cytokine production, but is more effective than wild-type HMGB1 in recruiting leukocytes in vivo. BoxA, a HMGB1 inhibitor, interferes with leukocyte recruitment but not with activation. We detected the different redox forms of HMGB1 ex vivo within injured muscle. HMGB1 is completely reduced at first and disulfide-bonded later. Thus, HMGB1 orchestrates both key events in sterile inflammation, leukocyte recruitment and their induction to secrete inflammatory cytokines, by adopting mutually exclusive redox states.
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影响因子：
11.2
作者：
Jube S;Rivera ZS;Bianchi ME;Powers A;Wang E;Pagano I;Pass HI;Gaudino G;Carbone M;Yang H
通讯作者：
Yang H
影响因子：
2.9
作者：
Knapp, S;Müller, S;Musco, G
通讯作者：
Musco, G
影响因子：
4.5
作者：
Biscetti, Federico;Ghirlanda, Giovanni;Flex, Andrea
通讯作者：
Flex, Andrea
DOI：
10.1523/jneurosci.2435-08.2008
发表时间：
2008-11-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Muhammad S;Barakat W;Stoyanov S;Murikinati S;Yang H;Tracey KJ;Bendszus M;Rossetti G;Nawroth PP;Bierhaus A;Schwaninger M
通讯作者：
Schwaninger M
影响因子：
5.4
作者：
UGUCCIONI, M;DAPUZZO, M;BAGGIOLINI, M
通讯作者：
BAGGIOLINI, M