title: Involvement of reactive oxygen species in ionizing radiation-induced upregulation of cell surface Toll-like receptor 2 and 4 expression in human monocytic cells.
abstract: Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and are indispensable for antibacterial and antiviral immunity. Our previous report showed that ionizing radiation increases the cell surface expressions of TLR2 and TLR4 and enhances their responses to agonists in human monocytic THP1 cells. The present study investigated how ionizing radiation increases the cell surface expressions of TLR2 and TLR4 in THP1 cells. The THP1 cells treated or not treated with pharmaceutical agents such as cycloheximide and N-acetyl-L-cysteine (NAC) were exposed to X-ray irradiation, following which the expressions of TLRs and mitogen-activated protein kinase were analyzed. X-ray irradiation increased the mRNA expressions of TLR2 and TLR4, and treatment with a protein synthesis inhibitor cycloheximide abolished the radiation-induced upregulation of their cell surface expressions. These results indicate that radiation increased those receptors through de novo protein synthesis. Furthermore, treatment with an antioxidant NAC suppressed not only the radiation-induced upregulation of cell surface expressions of TLR2 and TLR4, but also the radiation-induced activation of the c-Jun N-terminal kinase (JNK) pathway. Since it has been shown that the inhibitor for JNK can suppress the radiation-induced upregulation of TLR expression, the present results suggest that ionizing radiation increased the cell surface expressions of TLR2 and TLR4 through reactive oxygen species-mediated JNK activation.
authors.affiliation: Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000528:radiation effects; D002518:Ceramides / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000528:radiation effects; D014176:Protein Biosynthesis / Q000528:radiation effects; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation / Q000528:radiation effects*
chemical_list: D002518:Ceramides; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D048031:JNK Mitogen-Activated Protein Kinases; D000111:Acetylcysteine
keywords: Toll-like receptor; c-Jun N-terminal kinase; ionizing radiation; reactive oxygen species