Involvement of Reactive Oxygen Species in Ionizing Radiation-induced Upregulation of Cell Surface Toll-like Receptor 2 and 4 Expression in Human Monocytic Cells
Overview
Oncology
Radiology
Authors
Affiliations
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.
Saini S, Gurung P Immunol Rev. 2024; 329(1):e13409.
PMID: 39425547 PMC: 11742653. DOI: 10.1111/imr.13409.
Sharma G, Fish B, Frei A, Narayanan J, Gasperetti T, Scholler D Int J Radiat Oncol Biol Phys. 2022; 113(1):177-191.
PMID: 35093482 PMC: 9018504. DOI: 10.1016/j.ijrobp.2022.01.023.
Sato K, Iwasaki S, Yoshino H Int J Mol Sci. 2021; 22(24).
PMID: 34948029 PMC: 8704639. DOI: 10.3390/ijms222413233.
Roles of homologous recombination in response to ionizing radiation-induced DNA damage.
Nickoloff J, Sharma N, Allen C, Taylor L, Allen S, Jaiswal A Int J Radiat Biol. 2021; 99(6):903-914.
PMID: 34283012 PMC: 9629169. DOI: 10.1080/09553002.2021.1956001.
Sato Y, Yoshino H, Kashiwakura I, Tsuruga E Int J Mol Sci. 2021; 22(1).
PMID: 33401559 PMC: 7795940. DOI: 10.3390/ijms22010420.