title: Mediatory role of interleukin-6 in α smooth muscle actin induction and myofibroblast formation around silicone tissue expander.
abstract: Materials used for medical devices are usually tested for their biocompatibility, before use. However, it is known that long-term implantation in the body may lead to degradation of the material leading to an adverse tissue response. The failure of silicone breast implants due to excessive fibrosis and contracture has led to studies to delineate the cause of fibrosis around this material. To detect the biological moieties involved, conditioned media from RAW 264.7 macrophages seeded over commercially available silicone tissue expander material was added to L929 fibroblasts. Ultrahigh-molecular-weight polyethylene and tissue culture grade polystyrene served as the control materials. The gene expression of fibrogenic cytokines, interleukin-6 (IL-6), and transforming growth factor beta (TGFβ) in the RAW macrophages and myofibroblast marker alpha smooth muscle actin (αSMA) in L929 cells were quantitated by real time polymerase chain reaction. Protein expression analysis of αSMA was carried out by immunocytochemical staining and confocal microscopy. An in vitro degradation study of silicone expander material in pseudoextracellular fluid (PECF) and the αSMA expression in fibroblasts incubated with the silicone extract containing PECF has revealed the role of silicone leachants in induction of myofibroblasts. This in vitro expression study revealed the additional profibrotic role of IL-6 in fibroblast to myofibroblast transition and the synergy between material aspects and biomolecules in regulating fibrosis around Silicone implants. These findings may help in targeting newer biological moieties in the profibrotic pathway and in devising better manufacturing processes aiding the life of millions of patients.
authors.affiliation: Histopathology Laboratory, Division of Implant Biology, Bio Medical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Trivandrum, Kerala, India.
authors.forename: Josna
authors.initials: J
authors.lastname: Joseph
authors.forename: Kumary Thrikkovil
authors.initials: KT
authors.lastname: Variathu
authors.forename: Mira
authors.initials: M
authors.lastname: Mohanty
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045604:Extracellular Fluid / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018613:Microscopy, Confocal; D058628:Myofibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012828:Silicones / Q000494:pharmacology*; D015625:Tissue Expansion Devices; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D015850:Interleukin-6; D012828:Silicones; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse
keywords: fibrosis; interleukin-6; myofibroblast; silicone implants; α smooth muscle actin