Extracellular HMGB1 regulates multi-walled carbon nanotube-induced inflammation in vivo

Abstract Endotoxin is often used to activate NF-κB in vitro when assessing NLRP3 inflammasome activation by various exogenous particles including nanoparticles. However, the endogenous source of this signal 1 is unknown. High-mobility group box 1 (HMGB1) is known to play a critical role in acute lung injury, however the potential contribution of the alarmin HMGB1 to NLRP3 Inflammasome activation has not been determined in response to nanoparticles in vivo. In this study, the ability of multi-walled carbon nanotubes (MWCNT) to cause release of HMGB1 in vitro and in vivo, as well as the potential of HMGB1 to function as signal 1 in vitro and in vivo, was determined. HMGB1 activity in vivo was assessed by administration of HMGB1 neutralization antibodies following MWCNT exposure. Caspase-1−/− mice were utilized to elucidate the dependence of HMGB1 secretion on NLRP3 inflammasome activity. MWCNT exposure increased extracellular HMGB1 levels in primary alveolar macrophages from C57Bl/6 mice and C10 mouse epithelial cell culture supernatants, and in C57Bl/6 mouse lung lavage fluid. MWCNT-induced HMGB1 secretion was dependent upon caspase-1. HMGB1 increased MWCNT-induced IL-1β release from macrophages in vitro, and neutralization of extracellular HMGB1 reduced MWCNT-induced IL-1β secretion in vivo. HMGB1 neutralization was accompanied with overall decreased inflammation. In summary, this study suggests extracellular HMGB1 participates in NLRP3 inflammasome activity and regulates IL-1β associated sterile inflammation induced by MWCNT.

[1]  K. Tracey,et al.  HMG-1 as a late mediator of endotoxin lethality in mice. , 1999, Science.

[2]  D. Schwartz.  Inhaled endotoxin, a risk for airway disease in some people. , 2001, Respiration physiology.

[3]  F. Martinon,et al.  The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. , 2002, Molecular cell.

[4]  T. Misteli,et al.  Release of chromatin protein HMGB1 by necrotic cells triggers inflammation , 2002, Nature.

[5]  M. Bianchi,et al.  The nuclear protein HMGB1 is secreted by monocytes via a non‐classical, vesicle‐mediated secretory pathway , 2002, EMBO reports.

[6]  Masaki Tanaka,et al.  Contributions of high mobility group box protein in experimental and clinical acute lung injury. , 2004, American journal of respiratory and critical care medicine.

[7]  K. Tracey,et al.  Extracellular role of HMGB1 in inflammation and sepsis , 2004, Journal of internal medicine.

[8]  I. Douglas,et al.  HMGB1 contributes to the development of acute lung injury after hemorrhage. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[9]  E. Abraham,et al.  High mobility group box 1 protein interacts with multiple Toll-like receptors. , 2006, American journal of physiology. Cell physiology.

[10]  M. Morandi,et al.  Engineered carbon nanoparticles alter macrophage immune function and initiate airway hyper-responsiveness in the BALB/c mouse model , 2007 .

[11]  T. van der Poll,et al.  PULMONARY LEVELS OF HIGH-MOBILITY GROUP BOX 1 DURING MECHANICAL VENTILATION AND VENTILATOR-ASSOCIATED PNEUMONIA , 2007, Shock.

[12]  K. Kuwano,et al.  The role of high mobility group box1 in pulmonary fibrosis. , 2008, American journal of respiratory cell and molecular biology.

[13]  E. Abraham,et al.  HMGB1 Develops Enhanced Proinflammatory Activity by Binding to Cytokines1 , 2008, The Journal of Immunology.

[14]  Vincent Castranova,et al.  A biocompatible medium for nanoparticle dispersion , 2008 .

[15]  A. Sepulveda,et al.  Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis , 2009, Journal of leukocyte biology.

[16]  M. Huang,et al.  NLRP3 (NALP3, Cryopyrin) Facilitates In Vivo Caspase-1 Activation, Necrosis, and HMGB1 Release via Inflammasome-Dependent and -Independent Pathways1 , 2009, The Journal of Immunology.

[17]  U. Andersson,et al.  The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation , 2009, Journal of leukocyte biology.

[18]  A. Holian,et al.  Murine pulmonary inflammation model: a comparative study of anesthesia and instillation methods , 2010, Inhalation toxicology.

[19]  K. Tracey,et al.  Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia , 2010, The Journal of Immunology.

[20]  D. Wallace,et al.  Bacterial lipopolysaccharide enhances PDGF signaling and pulmonary fibrosis in rats exposed to carbon nanotubes. , 2010, American journal of respiratory cell and molecular biology.

[21]  H. Pass,et al.  Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation , 2010, Proceedings of the National Academy of Sciences.

[22]  M. Štros.  HMGB proteins: interactions with DNA and chromatin. , 2010, Biochimica et biophysica acta.

[23]  S. Akira,et al.  A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release , 2010, Proceedings of the National Academy of Sciences.

[24]  Grace Y Chen,et al.  Sterile inflammation: sensing and reacting to damage , 2010, Nature Reviews Immunology.

[25]  Per Axel Clausen,et al.  Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism. , 2011, ACS nano.

[26]  V. Deretic,et al.  Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β , 2011, The EMBO journal.

[27]  Vincent Castranova,et al.  Pulmonary fibrotic response to aspiration of multi-walled carbon nanotubes , 2011, Particle and Fibre Toxicology.

[28]  K. Tracey,et al.  Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release , 2012, The Journal of experimental medicine.

[29]  R. Keogh,et al.  Sputum Biomarkers and the Prediction of Clinical Outcomes in Patients with Cystic Fibrosis , 2012, PloS one.

[30]  Sang-Heon Cho,et al.  The role of high‐mobility group box‐1 (HMGB1) in the pathogenesis of asthma , 2012, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[31]  K. Tracey,et al.  Redox Modification of Cysteine Residues Regulates the Cytokine Activity of High Mobility Group Box-1 (HMGB1) , 2012, Molecular medicine.

[32]  K. Marcu,et al.  The IKKα-Dependent NF-κB p52/RelB Noncanonical Pathway Is Essential To Sustain a CXCL12 Autocrine Loop in Cells Migrating in Response to HMGB1 , 2012, The Journal of Immunology.

[33]  N. Wu,et al.  NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination , 2012, Inhalation toxicology.

[34]  Dirk E. Smith,et al.  IL-33 mediates multi-walled carbon nanotube (MWCNT)-induced airway hyper-reactivity via the mobilization of innate helper cells in the lung , 2012, Nanotoxicology.

[35]  Vincent Castranova,et al.  Distribution and fibrotic response following inhalation exposure to multi-walled carbon nanotubes , 2013, Particle and Fibre Toxicology.

[36]  J. Bonner,et al.  Nickel Nanoparticles cause exaggerated lung and airway remodeling in mice lacking the T-box transcription factor, TBX21 (T-bet) , 2014, Particle and Fibre Toxicology.

[37]  Andrij Holian,et al.  Effect of MWCNT size, carboxylation, and purification on in vitro and in vivo toxicity, inflammation and lung pathology , 2013, Particle and Fibre Toxicology.

[38]  B. Nagar,et al.  An Immunogenic Peptide in the A-box of HMGB1 Protein Reverses Apoptosis-induced Tolerance through RAGE Receptor*♦ , 2014, The Journal of Biological Chemistry.

[39]  D. Pisetsky.  The Expression of HMGB1 on Microparticles Released during Cell Activation and Cell Death In Vitro and In Vivo , 2014, Molecular medicine.

[40]  N. Wu,et al.  IL-1R signalling is critical for regulation of multi-walled carbon nanotubes-induced acute lung inflammation in C57Bl/6 mice , 2014, Nanotoxicology.

[41]  Huan Yang,et al.  Receptor for advanced glycation end products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway inflammation. , 2014, The Journal of allergy and clinical immunology.

[42]  E. Alnemri,et al.  Inflammasome Priming by Lipopolysaccharide Is Dependent upon ERK Signaling and Proteasome Function , 2014, The Journal of Immunology.