title: Toll-Like Receptor 4 Expression in Human Breast Implant Capsules: Localization and Correlation with Estrogen Receptors.
abstract: BACKGROUND
  Capsular contracture is the most common complication following breast augmentation and reconstruction. Myofibroblasts, which are specialized fibroblasts with contractile activity, are involved in its pathogenesis. Toll-like receptor 4 stimulation in fibroblasts induces transcription of genes involved in extracellular matrix remodeling and tissue repair; furthermore, it enhances sensitivity to transforming growth factor-β1 and promotes transition to myofibroblasts. 17β-Estradiol, by binding to its main receptors, α and/or β, increases the expression of toll-like receptor 4 and the production of proinflammatory mediators by macrophages; moreover, it promotes extracellular matrix production and myofibroblasts contraction and differentiation. The aim of the study was to investigate the expression of toll-like receptor 4 in breast implant capsules and its relationship with estrogen receptors.
  
  
  METHODS
  The study enrolled 30 women who underwent expander removal following breast reconstruction. Specimens were stained with hematoxylin and eosin, Masson trichrome, immunohistochemistry, and immunofluorescence for toll-like receptor 4, α-smooth muscle actin (a marker of myofibroblasts), estrogen receptor-α, and estrogen receptor-β.
  
  
  RESULTS
  Toll-like receptor 4 was expressed by fibroblasts and myofibroblasts of capsular tissue. Its expression positively correlated with estrogen receptor-β expression (p = 0.012). A positive correlation was found between estrogen receptor-β and α-smooth muscle actin expression (p = 0.037).
  
  
  CONCLUSIONS
  This study demonstrates the expression of toll-like receptor 4 in myofibroblasts of capsular tissue and its correlation with estrogen receptor-β positivity. Activation of toll-like receptor 4 and estrogen receptor-β, and their interplay, may be involved in myofibroblast differentiation and in the profibrotic pathogenic process underlying capsular contracture.
authors.affiliation: Rome, Italy From the Department of Plastic, Reconstructive and Aesthetic Surgery and the Center for Integrated Biomedical Research, Laboratory of Microscopic and Ultrastructural Anatomy, "Campus Bio-Medico di Roma" University.
authors.forename: Francesco
authors.initials: F
authors.lastname: Segreto
authors.forename: Simone
authors.initials: S
authors.lastname: Carotti
authors.forename: Daniele
authors.initials: D
authors.lastname: Tosi
authors.forename: Alfonso Luca
authors.initials: AL
authors.lastname: Pendolino
authors.forename: Giovanni Francesco
authors.initials: GF
authors.lastname: Marangi
authors.forename: Sergio
authors.initials: S
authors.lastname: Morini
authors.forename: Paolo
authors.initials: P
authors.lastname: Persichetti
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001707:Biopsy, Needle; D018427:Breast Implants / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D057910:Implant Capsular Contracture / Q000378:metabolism* / Q000473:pathology; D016462:Mammaplasty / Q000009:adverse effects* / Q000379:methods; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology; D011475:Prosthesis Failure; D011960:Receptors, Estrogen / Q000378:metabolism*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D011960:Receptors, Estrogen; D051197:Toll-Like Receptor 4