Abstract
Abstract Elevated Peroxiredoxin 1 (Prx1) expression is a poor prognostic factor in various cancers. Prx1 is an intracellular antioxidant and molecular chaperone protein that is non-classically secreted from transformed or stressed cells. Prx1 was found to increase the maturation state and secretion of pro-inflammatory cytokines from macrophages and dendritic cells in a Toll-Like Receptor (TLR4) dependent manner. Prx1 bound macrophages in a saturable, competitive, and TLR4 dependent manner. Prx1 immunoprecipitated and colocalized with TLR4. Extracellular Prx1 increased nuclear factor kappa B (NF-kB) translocation and DNA binding activity in a TLR4 dependent manner. In vivo, Prx1 injected intravenously in mice increased systemic interleukin 6 (IL-6) levels in a TLR4 dependent manner. Prx1 promotes innate immunity through the interaction in TLR4; however, the role of extracellular Prx1 in cancer remains undefined. Prx1 delayed tumor growth in prostate cancer models and additionally affected the numbers of CD11b+ Gr1HI F4/80+ tumor associated macrophages that have been identified as a myeloid derived suppressor cell population. This is the first time that extracellular Prx1 is demonstrated to interact with TLR4 on immune cells and that the interaction has consequential effects on macrophage populations and tumor progression.
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.
