Toll-like receptor 4 expression (TLR-4) in human breast implant capsules: localization and correlation with estrogen receptors

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.