Abstract
Matrilysin is a matrix metalloprotease that is overexpressed in cancer cells of epithelial origin and in normal tissues during events involving matrix remodeling such as the cycling endometrium. We previously observed that inflamed ductule and acinar epithelia in the prostate also overexpress matrilysin. The presence of infiltrating macrophages in these areas prompted us to determine if factors secreted from monocytes could induce matrilysin expression in a human prostatic cell line. Conditioned media collected from the monocyte cell line THP-1 following lipopolysaccharide treatment substantially induced matrilysin protein and mRNA expression in LNCaP prostate carcinoma cells. Matrilysin expression in LNCaP cells was also induced by recombinant interleukin (IL)-1 (50 pM), but not by equimolar concentrations of recombinant tumor necrosis factor-alpha or IL-6. The matrilysin-inducing activity of THP-1 conditioned medium was completely abrogated by preincubation with a neutralizing antibody to IL-1beta. Transient transfection analyses with a chimeric human matrilysin promoter-chloramphenicol acetyltransferase reporter construct demonstrated that IL-1beta activates transcription through the matrilysin promoter in LNCaP cells. This is the first report of matrilysin induction by an inflammatory cytokine in a cell line of epithelial origin, and the results suggest a potential mechanism for the overexpression of matrilysin in inflamed ducts and glands of the prostate.
Highlights
The matrix metalloproteases are a family of enzymes that degrade extracellular matrix proteins
The human prostate carcinoma cell line LNCaP was used because these cells express matrilysin protein in cell culture and have retained some features of normal prostate epithelial cells including androgen responsiveness and secretion of prostate-specific antigen
We have demonstrated that IL-1 secreted from the THP-1 monocyte cell line induces expression of the matrix metalloprotease matrilysin by the prostate carcinoma cell line LNCaP
Summary
The matrix metalloproteases are a family of enzymes that degrade extracellular matrix proteins. The purpose of the work reported here was to determine if factors secreted from monocytic cells could induce matrilysin expression in a prostatic cell line and, if so, by what mechanism. We report that IL-1 secreted from monocytic cells induces matrilysin expression in LNCaP cells and that the mechanism of this induction involves an increase in matrilysin gene transcription.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
