Abstract
High mobility group box-1 (HMGB1) mainly belongs to the non-histone DNA-binding protein. It has been studied as a nuclear protein that is present in eukaryotic cells. From the HMG family, HMGB1 protein has been focused particularly for its pivotal role in several pathologies. HMGB-1 is considered as an essential facilitator in diseases such as sepsis, collagen disease, atherosclerosis, cancers, arthritis, acute lung injury, epilepsy, myocardial infarction, and local and systemic inflammation. Modulation of HMGB1 levels in the human body provides a way in the management of these diseases. Various strategies, such as HMGB1-receptor antagonists, inhibitors of its signalling pathway, antibodies, RNA inhibitors, vagus nerve stimulation etc. have been used to inhibit expression, release or activity of HMGB1. This review encompasses the role of HMGB1 in various pathologies and discusses its therapeutic potential in these pathologies.
Keywords: High mobility group box-1, cytokine mediator, inflammatory disease, cancer, sepsis, therapeutics.
Graphical Abstract
[http://dx.doi.org/10.1016/j.it.2012.10.005] [PMID: 23116548]
[http://dx.doi.org/10.1016/j.bbi.2017.10.008] [PMID: 29031614]
[http://dx.doi.org/10.1016/j.smim.2018.02.011] [PMID: 29530410]
[http://dx.doi.org/10.1016/j.autrev.2010.05.015] [PMID: 20546955]
[http://dx.doi.org/10.1016/j.jss.2009.11.708] [PMID: 20338589]
[http://dx.doi.org/10.1016/j.cca.2018.04.042] [PMID: 29730397]
[http://dx.doi.org/10.1016/j.bbi.2018.06.012] [PMID: 29920330]
[http://dx.doi.org/10.1016/j.bbrc.2013.10.085] [PMID: 24427810]
[http://dx.doi.org/10.1189/jlb.1212662] [PMID: 23446148]
[http://dx.doi.org/10.1016/j.bbrc.2017.11.083] [PMID: 29146189]
[http://dx.doi.org/10.1016/j.bbi.2017.11.018] [PMID: 29175543]
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.12.016] [PMID: 19150066]
[http://dx.doi.org/10.1016/j.jss.2018.02.049] [PMID: 29907203]
[http://dx.doi.org/10.1016/j.rmed.2009.05.019] [PMID: 19535236]
[http://dx.doi.org/10.3892/ijmm.2013.1286] [PMID: 23440289]
[http://dx.doi.org/10.1016/j.virol.2018.09.001] [PMID: 30216776]
[http://dx.doi.org/10.1073/pnas.1316925111] [PMID: 24469805]
[http://dx.doi.org/10.4161/auto.6.8.13651] [PMID: 20935509]
[http://dx.doi.org/10.1073/pnas.1320808110] [PMID: 24302768]
[http://dx.doi.org/10.1053/j.gastro.2013.12.015] [PMID: 24361123]
[http://dx.doi.org/10.1002/hep.26976] [PMID: 24375466]
[http://dx.doi.org/10.1016/j.tjog.2018.02.008] [PMID: 29673663]
[http://dx.doi.org/10.4049/jimmunol.181.7.5015] [PMID: 18802105]
[http://dx.doi.org/10.1126/science.1240248] [PMID: 23887873]
[http://dx.doi.org/10.1038/nature11290] [PMID: 22801494]
[http://dx.doi.org/10.1586/1744666X.2014.909730] [PMID: 24746113]
[http://dx.doi.org/10.1016/j.phrs.2016.06.031] [PMID: 27378565]
[http://dx.doi.org/10.1038/aps.2011.151] [PMID: 22158106]
[http://dx.doi.org/10.1016/j.yexmp.2012.05.006] [PMID: 22609241]
[http://dx.doi.org/10.1002/hep.26294] [PMID: 23390034]
[http://dx.doi.org/10.1152/ajpgi.00151.2013] [PMID: 24091596]
[http://dx.doi.org/10.1146/annurev-immunol-030409-101323] [PMID: 21219181]
[http://dx.doi.org/10.1016/S0140-6736(12)61815-7] [PMID: 23472921]
[http://dx.doi.org/10.1073/pnas.1301218110] [PMID: 23898178]
[http://dx.doi.org/10.1038/mt.2013.195] [PMID: 23985697]
[http://dx.doi.org/10.1038/nature10400] [PMID: 21921917]
[http://dx.doi.org/10.1038/nm.3368] [PMID: 24097189]
[http://dx.doi.org/10.1038/ni1457] [PMID: 17417641]
[http://dx.doi.org/10.1189/jlb.0306180] [PMID: 16966386]
[http://dx.doi.org/10.1189/jlb.0306171] [PMID: 17035340]
[http://dx.doi.org/10.1038/sj.emboj.7601552] [PMID: 17268551]
[http://dx.doi.org/10.1083/jcb.152.6.1197] [PMID: 11257120]
[http://dx.doi.org/10.1097/01.shk.0000225404.51320.82] [PMID: 16878026]
[http://dx.doi.org/10.1182/blood-2006-09-044776] [PMID: 17548579]
[http://dx.doi.org/10.1126/science.1168988]
[http://dx.doi.org/10.1172/JCI22782] [PMID: 15841214]
[http://dx.doi.org/10.1016/0014-4827(92)90194-D] [PMID: 1369684]
[http://dx.doi.org/ [http://10.1182/blood-2002-05-1300] [PMID: 12456506]
[http://dx.doi.org/10.2119/molmed.2009.00062]
[http://dx.doi.org/10.1084/jem.20111739] [PMID: 22370717]
[http://dx.doi.org/10.1084/jem.20120189] [PMID: 22869893]
[http://dx.doi.org/10.2119/molmed.2011.00389] [PMID: 22105604]
[http://dx.doi.org/10.1038/emboj.2012.328] [PMID: 23222484]
[http://dx.doi.org/10.1038/nature09663] [PMID: 21124315]
[http://dx.doi.org/10.1016/j.immuni.2009.02.005] [PMID: 19362020]
[http://dx.doi.org/10.1038/ni.1960] [PMID: 21057511]
[http://dx.doi.org/10.1016/j.cca.2006.04.016] [PMID: 16797518]
[http://dx.doi.org/10.1002/lt.21573] [PMID: 18825712]
[http://dx.doi.org/10.1093/emboj/20.16.4337] [PMID: 11500360]
[http://dx.doi.org/10.1189/jlb.0306196] [PMID: 17060363]
[http://dx.doi.org/10.1002/art.21488] [PMID: 16320336]
[http://dx.doi.org/10.1177/0961203307081895] [PMID: 17895302]
[http://dx.doi.org/10.1007/s11010-009-0305-0] [PMID: 19876719]
[http://dx.doi.org/10.1002/art.21969] [PMID: 16802368]
[http://dx.doi.org/10.1002/art.20220] [PMID: 15146429]
[http://dx.doi.org/10.1186/ar3332] [PMID: 21548924]
[http://dx.doi.org/10.1017/S1462399408000884] [PMID: 18980707]
[http://dx.doi.org/10.1126/science.282.5396.2085] [PMID: 9851930]
[http://dx.doi.org/10.1038/ni809] [PMID: 12055629]
[http://dx.doi.org/10.2119/molmed.2012.00306] [PMID: 23508573]
[http://dx.doi.org/10.1038/ni.1976] [PMID: 21170027]
[http://dx.doi.org/10.1126/science.285.5425.248] [PMID: 10398600]
[http://dx.doi.org/10.1073/pnas.2434651100] [PMID: 14695889]
[http://dx.doi.org/10.1189/jlb.1104648] [PMID: 15734795]
[http://dx.doi.org/10.1164/ajrccm.164.10.2106117] [PMID: 11734424]
[http://dx.doi.org/10.1073/pnas.1216195109] [PMID: 23213216]
[http://dx.doi.org/10.1002/art.10859] [PMID: 12687539]
[http://dx.doi.org/10.1002/art.10540] [PMID: 12384917]
[http://dx.doi.org/10.1002/art.11028] [PMID: 12794838]
[http://dx.doi.org/10.4049/jimmunol.1203301] [PMID: 23616573]
[http://dx.doi.org/10.1016/j.neuropharm.2011.06.026] [PMID: 21752338]
[http://dx.doi.org/10.1155/2015/946748] [PMID: 26078984]
[http://dx.doi.org/10.4049/jimmunol.1000803] [PMID: 20802146]
[http://dx.doi.org/10.1089/ars.2015.6397] [PMID: 26493086]
[http://dx.doi.org/10.1038/jcbfm.2010.129] [PMID: 20700129]
[http://dx.doi.org/10.1523/JNEUROSCI.2439-14.2015] [PMID: 25589753]
[http://dx.doi.org/10.1523/JNEUROSCI.2435-08.2008] [PMID: 19005067]
[http://dx.doi.org/10.1016/j.autrev.2012.03.007] [PMID: 22495229]
[http://dx.doi.org/10.1016/j.egja.2017.09.005]
[http://dx.doi.org/10.1016/j.bbadis.2017.07.012] [PMID: 28716707]
[http://dx.doi.org/10.1016/j.ijcard.2017.11.038] [PMID: 29169909]
[http://dx.doi.org/10.1016/S0002-9440(10)62344-9] [PMID: 15793304]
[http://dx.doi.org/10.4049/jimmunol.176.1.12] [PMID: 16365390]
[http://dx.doi.org/10.1161/01.RES.0000257774.55970.f4] [PMID: 17218606]
[http://dx.doi.org/10.1152/ajpheart.00910.2007] [PMID: 18223193]
[http://dx.doi.org/10.1253/circj.72.1012] [PMID: 18503231]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.769331] [PMID: 18574060]
[http://dx.doi.org/10.1111/j.1538-7836.2006.02255.x] [PMID: 17239166]
[http://dx.doi.org/10.1016/j.cardfail.2008.11.010] [PMID: 19398086]
[http://dx.doi.org/10.1016/j.jacc.2004.05.083] [PMID: 15464336]
[http://dx.doi.org/10.1016/S0735-1097(01)01721-1] [PMID: 11788214]
[http://dx.doi.org/10.1161/01.CIR.0000147233.10318.23] [PMID: 15533863]
[http://dx.doi.org/10.1161/01.RES.0000130526.20854.fa] [PMID: 15217919]
[http://dx.doi.org/10.1016/S0008-6363(01)00434-5] [PMID: 11744011]
[http://dx.doi.org/10.1084/jem.20042614] [PMID: 15795240]
[http://dx.doi.org/10.1523/JNEUROSCI.3815-05.2006] [PMID: 16775128]
[http://dx.doi.org/10.1084/jem.192.4.565] [PMID: 10952726]
[http://dx.doi.org/10.1038/nri1594] [PMID: 15803152]
[http://dx.doi.org/10.1093/cvr/cvn291] [PMID: 18984601]
[http://dx.doi.org/10.1038/nature06005] [PMID: 17653185]
[http://dx.doi.org/10.1016/j.intimp.2015.10.015] [PMID: 26541861]
[http://dx.doi.org/10.1038/ni1261] [PMID: 16200068]
[http://dx.doi.org/10.1016/j.immuni.2013.12.006] [PMID: 24439264]
[http://dx.doi.org/10.1002/eji.201141879] [PMID: 21928275]
[http://dx.doi.org/10.3389/fimmu.2015.00422] [PMID: 26347745]
[http://dx.doi.org/10.1159/000460513] [PMID: 28222432]
[http://dx.doi.org/10.1038/s41598-017-01325-y] [PMID: 28446773]
[http://dx.doi.org/10.1080/02699052.2016.1217045] [PMID: 27819487]
[http://dx.doi.org/10.1016/j.bbi.2017.10.008] [PMID: 29031614]
[http://dx.doi.org/10.1038/srep46243] [PMID: 28393932]
[http://dx.doi.org/10.1016/j.bbi.2017.02.002] [PMID: 28167116]
[http://dx.doi.org/10.1093/brain/awx117] [PMID: 28575153]
[http://dx.doi.org/10.1038/nm.2127] [PMID: 20348922]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0495] [PMID: 23723299]
[http://dx.doi.org/10.18632/oncotarget.9496] [PMID: 27223258]
[http://dx.doi.org/10.1007/5584_2015_115]
[http://dx.doi.org/10.2337/dc09-1799] [PMID: 20067962]
[http://dx.doi.org/10.1111/j.1755-5922.2009.00077.x] [PMID: 19426249]
[http://dx.doi.org/10.1038/cdd.2010.191] [PMID: 21311563]
[PMID: 26617792]
[http://dx.doi.org/10.1016/j.bbrc.2016.10.052] [PMID: 27769864]
[http://dx.doi.org/10.1080/15216540701636287] [PMID: 17885832]
[http://dx.doi.org/10.1016/S0014-2999(02)01828-9] [PMID: 12106797]
[http://dx.doi.org/10.4103/1110-1067.161290]
[PMID: 22432086]
[http://dx.doi.org/10.3109/10428194.2011.616962] [PMID: 21864037]
[http://dx.doi.org/10.1155/2018/2754941] [PMID: 29651425]
[http://dx.doi.org/10.1016/j.jhep.2014.06.033] [PMID: 25010260]
[http://dx.doi.org/10.1002/hep.26420] [PMID: 23532963]
[http://dx.doi.org/10.1002/hep.29663] [PMID: 29149457]
[http://dx.doi.org/10.3892/ijo.2014.2285] [PMID: 24481712]
[http://dx.doi.org/10.3892/mmr.2013.1362] [PMID: 23467607]
[http://dx.doi.org/10.3390/ijms15058699] [PMID: 24837834]
[PMID: 12383549]
[http://dx.doi.org/10.1006/gyno.2000.5732] [PMID: 10739706]
[http://dx.doi.org/10.2217/fon.13.65] [PMID: 23902245]
[http://dx.doi.org/10.4103/1477-3163.83937] [PMID: 21886458]
[http://dx.doi.org/10.3892/ol.2017.6965] [PMID: 29113279]