Ionizing radiation affects the expression of Toll-like receptors 2 and 4 in human monocytic cells through c-Jun N-terminal kinase activation.

Pattern recognition receptors recognize pathogen-associated molecular patterns. Among these, Toll-like receptors (TLRs) have well-characterized roles in antibacterial and antiviral immunity. In the present study, the effects of ionizing radiation on the expression of TLRs and cellular responses to ligands were investigated in THP1 monocytes (human monocytic leukemia cells) and THP1-derived macrophage cells (macrophage-like cells), which are induced by culturing in the presence of phorbol 12-myristate 13-acetate. TLR2 and TLR4 expression was detected in THP1 and macrophage-like cells. X-irradiation caused increased expression of these TLRs in THP1 and decreased expression in macrophage-like cells. Responses to FSL-1 (TLR2 ligand) and lipopolysaccharide (LPS, TLR4 ligand) were estimated by determining the induction of tumor necrosis factor-α (TNF-α). After FSL-1 or LPS stimulation, TNF-α induction was greater in X-irradiated THP1 monocytes than in non-irradiated cells. However, although TNF-α expression was not affected by X-irradiation in macrophage-like cells, the expression of LPS-inducible interferon-β was lower following X-irradiation of macrophage-like cells. To clarify the mechanisms of TLR2 and TLR4 regulation by X-irradiation, expression of mitogen-activated protein kinase was investigated. These experiments showed that c-Jun N-terminal kinase (JNK) mediated increases in TLR expression in X-irradiated THP1 monocytes and decreases in TLR expression in X-irradiated macrophage-like cells. This study demonstrates that ionizing radiation modulates ligand-responsive TLR expression through the JNK pathway, depending on differentiation state. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Citation

Hironori Yoshino, Kanae Chiba, Takahiro Saitoh, Ikuo Kashiwakura. Ionizing radiation affects the expression of Toll-like receptors 2 and 4 in human monocytic cells through c-Jun N-terminal kinase activation. Journal of radiation research. 2014 Sep;55(5):876-84

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PMID: 24927726

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