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Cellular source and proinflammatory roles of high‐mobility group box 1 in surgically injured rat vocal folds
Author(s) -
LiJessen Nicole Y. K.,
Powell Michael,
Choi AeJin,
Lee ByungJoo,
Thibeault Susan L.
Publication year - 2017
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.26333
Subject(s) - hmgb1 , proinflammatory cytokine , extracellular matrix , medicine , vocal folds , tumor necrosis factor alpha , extracellular , fibroblast , cytokine , myofibroblast , microbiology and biotechnology , pathology , inflammation , immunology , biology , anatomy , cell culture , genetics , larynx , fibrosis
Objectives/Hypothesis 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. Study Design Prospective animal study. Methods 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. Results 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. Conclusions 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. Level of Evidence NA Laryngoscope , 127:E193–E200, 2017