title: Dedifferentiation of prostate smooth muscle cells in response to bacterial LPS.
abstract: BACKGROUND
  Prostate smooth muscle cells (SMCs) are strongly involved in the development and progression of benign prostatic hyperplasia and prostate cancer. However, their participation in prostatitis has not been completely elucidated. Thus, we aimed to characterize the response of normal SMC to bacterial lipopolysaccharide (LPS).
  
  
  METHODS
  Primary prostate SMCs from normal rats were stimulated with LPS (0.1, 1, or 10 µg/ml) for 24 or 48 hr. The phenotype was evaluated by electron microscopy, immunofluorescence, and Western blot of SMCα-actin (ACTA2), calponin, vimentin, and tenascin-C, while the innate immune response was assessed by immunodetection of TLR4, CD14, and nuclear NF-κB. The secretion of TNFα and IL6 was determined using ELISA.
  
  
  RESULTS
  Bacterial LPS induces SMCs to develop a secretory phenotype including dilated rough endoplasmic reticulum cisternae with well-developed Golgi complexes. Furthermore, SMCs displayed a decrease in ACTA2 and calponin, and an increase in vimentin levels after LPS challenge. The co-expression of ACTA2 and vimentin, together with the induction of tenascin-C expression indicate that a myofibroblastic-like phenotype was induced by the endotoxin. Moreover, LPS elicited a TLR4 increase, with a peak in NF-κB activation occurring after 10 min of treatment. Finally, LPS stimulated the secretion of IL6 and TNFα.
  
  
  CONCLUSIONS
  Prostate SMCs are capable of responding to LPS in vitro by dedifferentiating from a contractile to a miofibroblastic-like phenotype and secreting cytokines, with the TLR4 signaling pathway being involved in this response. In this way, prostate SMCs may contribute to the pathophysiology of inflammatory diseases by modifying the epithelial-stromal interactions.
authors.affiliation: Center of Electron Microscopy, School of Medical Sciences, National University of Cordoba, Cordoba, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Leimgruber
authors.forename: Amado A
authors.initials: AA
authors.lastname: Quintar
authors.forename: Liliana D V
authors.initials: LD
authors.lastname: Sosa
authors.forename: Luciana N
authors.initials: LN
authors.lastname: García
authors.forename: Mauricio
authors.initials: M
authors.lastname: Figueredo
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Maldonado
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054337:Cell Dedifferentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007113:Immunity, Innate / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha