Dynamic Biomechanical Strain Inhibits IL-1β–induced Inflammation in Vocal Fold Fibroblasts

  • Ryan C. Branski
    Correspondence
    Address correspondence and reprint requests to Ryan C. Branski, PhD, Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
    Affiliations
    Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
    Search for articles by this author
  • Priyangi Perera
    Affiliations
    Section of Oral Biology, The Ohio State University, Columbus, Ohio
    Search for articles by this author
  • Katherine Verdolini
    Affiliations
    Communication Science and Disorders, University of Pittsburgh, Pittsburgh, Pennsylvania

    University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh, Pennsylvania

    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania
    Search for articles by this author
  • Clark A. Rosen
    Affiliations
    Communication Science and Disorders, University of Pittsburgh, Pittsburgh, Pennsylvania

    University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh, Pennsylvania

    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania
    Search for articles by this author
  • Patricia A. Hebda
    Affiliations
    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania

    Otolaryngology Wound Healing Laboratory, Children's Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
    Search for articles by this author
  • Sudha Agarwal
    Affiliations
    Section of Oral Biology, The Ohio State University, Columbus, Ohio

    Department of Orthopedics, The Ohio State University, Columbus, Ohio
    Search for articles by this author

      Summary

      Despite the fact that vocal folds are subjected to extensive mechanical forces, the role of mechanical strain in vocal fold wound healing has been overlooked. Recent studies on other tissues have demonstrated that low physiological levels of mechanical forces are beneficial to injured tissues, reduce inflammation, and induce synthesis of matrix-associated proteins essential for enhanced wound healing. In this study, we speculated that mechanical strain of low magnitudes also attenuates the production of inflammatory mediators and alters the extracellular matrix synthesis to augment wound healing in cultured vocal fold fibroblasts. To test this hypothesis, fibroblasts from rabbit vocal folds were isolated and exposed to various magnitudes of cyclic tensile strain (CTS) in the presence or absence of interleukin-1β (IL-1β). Results suggest that IL-1β activates proinflammatory gene transcription in vocal fold fibroblasts. Furthermore, CTS abrogates the IL-1β–induced proinflammatory gene induction in a magnitude-dependent manner. In addition, CTS blocks IL-1β–mediated inhibition of collagen type I synthesis, and thereby upregulates collagen synthesis in the presence of IL-1β. These findings are the first to reveal the potential utility of low levels of mechanical signals in vocal fold wound healing, and support the emerging on vivo data suggesting beneficial effects of vocal exercise on acute phonotrauma.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Voice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gunter H.E.
        Modeling mechanical stresses as a factor in the etiology of benign vocal fold lesions.
        J Biomech. 2004; 37: 1119-1124
        • Gray S.D.
        Benign pathologic responses of the larynx.
        NCVS Status Prog Rep. 1997; 11: 135-148
        • Krischke S.
        • Weigelt S.
        • Hoppe U.
        • Kollner V.
        • Klotz M.
        • Eysholdt U.
        • Rosanowski F.
        Quality of life in dysphonic patients.
        J Voice. 2005; 19: 132-137
        • Rasch T.
        • Gunther S.
        • Hoppe U.
        • Eysholdt U.
        • Rosanowski F.
        Voice-related quality of life in organic and functional voice disorders.
        Logoped Phoniatr Vocol. 2005; 30: 9-13
        • Colton R.
        • Casper J.K.
        Understanding Voice Problems: A Physiological Perspective for Diagnosis and Treatment.
        2nd ed. Williams & Wilkins, Baltimore, MD1996
        • Boone D.R.
        • McFarlane S.C.
        The Voice and Voice Therapy.
        5th ed. Prentice-Hall, Inc, Englewood Cliffs, NJ1994
        • Froeschels E.
        Hygiene of the voice.
        Arch Otolaryngol. 1943; 38: 122-130
        • Roy N.
        • Weinrich B.
        • Gray S.D.
        • et al.
        Voice amplification versus vocal hygiene instruction for teachers with voice disorders: a treatment outcomes study.
        J Speech Lang Hear Res. 2002; 45: 625-638
        • Roy N.
        • Weinrich B.
        • Gray S.D.
        • et al.
        An evaluation of the effects of two treatment approaches for teachers with voice disorders: a prospective randomized clinical trial.
        J Speech Lang Hear Res. 2001; 44: 286-296
        • Berry D.A.
        • Verdolini K.
        • Montequin D.W.
        • Hess M.M.
        • Chan R.W.
        • Titze I.R.
        A quantitative output-cost ratio in voice production.
        J Speech Lang Hear Res. 2001; 44: 29-37
        • Jiang J.J.
        • Titze I.R.
        Measurement of vocal fold intraglottal pressure and impact stress.
        J Voice. 1994; 8: 132-144
        • Titze I.R.
        Mechanical stress in phonation.
        J Voice. 1994; 8: 99-105
        • Verdolini-Marston K.
        • Burke M.K.
        • Lessac A.
        • Glaze L.
        • Caldwell E.
        Preliminary study of two methods of treatment for laryngeal nodules.
        J Voice. 1995; 9: 74-85
        • Verdolini K.
        Resonant voice therapy.
        in: Stemple J.C. Voice Therapy: Clinical Studies. Singular Publishing Group, San Deigo, CA2000: 46-62
        • Deschner J.
        • Hofman C.R.
        • Piesco N.P.
        • Agarwal S.
        Signal transduction by mechanical strain in chondrocytes.
        Curr Opin Clin Nutr Metab Care. 2003; 6: 289-293
        • Ferretti M.
        • Srinivasan A.
        • Deschner J.
        • et al.
        Anti-inflammatory effects of continuous passive motion on meniscal fibrocartilage.
        J Orthop Res. 2005; 23: 1165-1171
        • Branski R.C.
        • Rosen C.A.
        • Verdolini K.
        • Hebda P.A.
        Cytokine analysis of acute wound healing in the larynx: a rabbit model.
        J Voice. 2005; 19: 283-289
        • Verdolini K.
        • Rosen C.A.
        • Branski R.C.
        • Hebda P.A.
        Shifts in biochemical markers associated with wound healing in laryngeal secretions following phonotrauma: a preliminary study.
        Ann Otol Rhinol Laryngol. 2003; 112: 1021-1025
        • Agarwal S.
        Low magnitude of tensile strain inhibits IL-1beta dependent induction of pro-inflammatory cytokines and induces synthesis of IL-10 in human periodontal ligament cells in vitro.
        J Dent Res. 2001; 80: 1416-1420
        • Agarwal S.
        • Long P.
        • Gassner R.
        • Piesco N.P.
        • Buckley N.J.
        Cyclic tensile strain suppresses catabolic effects of interleukin-1beta in fibrochondrocytes from the temporomandibular joint.
        Arthritis Rheum. 2001; 44: 608-617
        • Gassner R.
        • Buckley M.J.
        • Georgescu H.
        • et al.
        Cyclic tensile stress exerts anti-inflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase.
        J Immunol. 1999; 163: 2187-2192
        • Long P.
        • Liu F.
        • Piesco N.P.
        • Kapur R.
        • Agarwal S.
        Signalling by mechanical strain involves transcriptional regulation of proinflammatory genes in human periodontal ligament cells in vitro.
        Bone. 2002; 30: 547-552
        • Agarwal S.
        • Long P.
        • Seyedain A.
        • Piesco N.
        • Shree A.
        • Gassner R.
        A central role for nuclear factor-KB pathway in the antiinflammatory and proinflammatory actions of mechanical strain.
        FASEB J. 2003; 17: 899-901
      1. Verdolini K, Rosen CA, Urban E, Branski, RC, Steinhauer K, Hebda PA. The effect of targeted vocal exercise on recovery from acute inflammation. Presented at: The Voice Foundation's 34th Annual Symposium: Care of the Professional Voice; 2005; Philadelphia, PA.

        • Gray S.D.
        • Titze I.R.
        • Chan R.
        • Hammond T.H.
        Vocal fold proteoglycans and their influence on biomechanics.
        Laryngoscope. 1999; 109: 845-854
        • Thibeault S.L.
        • Gray S.D.
        • Bless D.M.
        • Chan R.W.
        • Ford C.N.
        Histologic and rheologic characterization of vocal fold scarring.
        J Voice. 2002; 16: 96-104
        • Deschner J.
        • Rath-Deschner B.
        • Agarwal S.
        Regulation of matrix metalloproteinase expression by dynamic tensile strain in rat fibrochondrocytes.
        Osteoarthritis Cartilage. 2006; 14: 264-272
        • Schmidt H.H.W.
        Determination of nitric oxide via measurement of nitrite and nitrate in culture media.
        Biochemica. 1995; : 22
        • Branski R.C.
        • Rosen C.A.
        • Verdolini K.
        • Hebda P.A.
        Markers of wound healing in vocal fold secretions from patients with laryngeal pathology.
        Ann Otol Rhinol Laryngol. 2004; 113: 23-29
        • Titze I.R.
        • Hitchcock R.W.
        • Broadhead K.
        • Web K.
        • Li W.
        • Gray S.D.
        • Tresco P.A.
        Design and validation of a bioreactor for engineering vocal fold tissues under combined tensile and vibrational stresses.
        J Biomech. 2004; 37: 1521-1529
        • Dohar J.E.
        • Klein E.C.
        • Betsch J.L.
        • Hebda P.A.
        Fetal airway repair: a new frontier.
        Arch Otolaryngol Head Neck Surg. 1998; 124: 25-29