Role of human <scp>RNase</scp> 7 in neuronal and glial cell models: moving towards an unexpected new functional link

Human ribonuclease 7 (RNase 7), originally isolated from skin, is a member of the RNase A Superfamily and primarily known to be among the endogenous proteins with the most pronounced antimicrobial properties. Nevertheless, to date, studies on this enzyme are mostly limited to its antimicrobial effects on epithelial tissue, which is surprising considering the numerous districts of the human body potentially susceptible to infections. This inference inspired the present work, which is mainly dedicated to uncovering new roles of the RNase 7 in human cells that have not yet been explored in relation to this antimicrobial agent: neuronal cells. In this context, we decided to address possible host defense properties of RNase 7 in the nervous system, and to do this, we have selected both neuroblastoma SH-SY5Y and glioblastoma U-87 MG cells as experimental models. As a result, we found that, in addition to endogenously expressing RNase 7 under altered growth conditions, both cell lines are also responsive to its administration. More specifically, we highlighted for the first time that recombinant RNase 7 reduces the expression levels of pro-inflammatory cytokines, the release of nitric oxide, and the production of reactive oxygen species in LPS-stimulated SH-SY5Y and U-87 MG cells, contributing to their innate immune response. Moreover, here we highlighted that internalized recombinant RNase 7 can contribute to bacterial clearance in both SH-SY5Y and U-87 MG. These findings extend the functional role of RNase 7 beyond epithelia, indicating its potential involvement in neuroimmune regulation and suggesting novel therapeutic implications.