title: Cellular source and proinflammatory roles of high-mobility group box 1 in surgically injured rat vocal folds.
abstract: High-mobility group box 1 (HMGB1) is a chromatin-binding protein located in the cell nucleus. Following injury, immunocompetent cells secrete HMGB1 to the extracellular milieu under the stimulation of proinflammatory cytokines. Extracellular HMGB1 acts a danger signal that instigates the innate immunity and tissue repair. We previously reported HMGB1 in the vocal fold extracellular compartment between day 3 and day 7 following surgical injury. In this study, we further investigated the cell source of HMGB1 and the relationship of proinflammatory cytokine expression and HMGB1 translocation in wounded vocal folds.
  
  
  
  Prospective animal study.
  
  
  
  Bilateral vocal fold injury was performed on 122 Sprague-Dawley rats. An additional 18 rats served as uninjured controls. Animals were sacrificed at multiple time points up to 4 weeks after surgery. Immunohistochemical costaining was performed to identify the cell source of HMGB1. Cell markers ED1, fibroblast-specific protein 1 (FSP1), and alpha smooth muscle actin (α-SMA) were used to identify macrophages, fibroblasts, and myofibroblasts, respectively. Enzyme-linked immunosorbent assays were performed to measure cytokine levels of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in vocal fold tissue.
  
  
  
  Costaining of HMGB1 was strong with ED1 and FSP1 but was minimal with α-SMA in injured vocal folds. Compared to uninjured controls, IL-1β and TNF-α expression increased significantly the first 2 days after injury.
  
  
  
  Macrophages and fibroblasts were a major cell source of vocal fold HMGB1. Translocation of HMGB1 may be an active response to the early accumulation of IL-1β and TNF-α in the wounded vocal folds.
  
  
  
  NA Laryngoscope, 127:E193-E200, 2017.
authors: School of Communication Sciences and Disorders, McGill University, Montreal, Quebec, Canada.
authors: Nicole Y K
authors: NYK
authors: Li-Jessen
authors: Virginia Tech Carillon Research Institute, Roanoke, Virginia, U.S.A.
authors: Michael
authors: M
authors: Powell
authors: Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, U.S.A.
authors: Ae-Jin
authors: AJ
authors: Choi
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University School of Medicine, Busan, Korea.
authors: Byung-Joo
authors: BJ
authors: Lee
authors: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A.
authors: Susan L
authors: SL
authors: Thibeault
mesh_terms: D000199:Actins; D000818:Animals; D002135:Calcium-Binding Proteins; D053358:Ectodermal Dysplasia 1, Anhidrotic; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014827:Vocal Cords / Q000166:cytology / Q000276:immunology* / Q000293:injuries
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; C579666:FSP1 protein, rat; D024243:HMGB1 Protein; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: HMGB1; cytokines; inflammation; vocal folds; wound healing