Yoshino Hironori, Chiba Kanae, Saitoh Takahiro, Kashiwakura Ikuo
Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan
J Radiat Res. 2014 Sep;55(5):876-84. doi: 10.1093/jrr/rru040. Epub 2014 Jun 13.
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.
模式识别受体可识别病原体相关分子模式。其中，Toll样受体（TLRs）在抗菌和抗病毒免疫中具有明确的作用。在本研究中，我们研究了电离辐射对THP1单核细胞（人单核细胞白血病细胞）和THP1衍生的巨噬细胞（巨噬细胞样细胞）中TLRs表达及细胞对配体反应的影响，这些细胞是在佛波酯12 -肉豆蔻酸酯13 -乙酸酯存在的情况下培养诱导产生的。在THP1和巨噬细胞样细胞中检测到了TLR2和TLR4的表达。X射线照射导致THP1中这些TLRs的表达增加，而在巨噬细胞样细胞中表达降低。通过测定肿瘤坏死因子-α（TNF-α）的诱导情况来评估对FSL - 1（TLR2配体）和脂多糖（LPS，TLR4配体）的反应。在FSL - 1或LPS刺激后，X射线照射的THP1单核细胞中TNF-α的诱导作用比未照射细胞更强。然而，尽管TNF-α的表达在X射线照射的巨噬细胞样细胞中不受影响，但巨噬细胞样细胞经X射线照射后，LPS诱导的干扰素-β的表达较低。为了阐明X射线照射对TLR2和TLR4调控的机制，我们研究了丝裂原活化蛋白激酶的表达。这些实验表明，c - Jun氨基末端激酶（JNK）介导了X射线照射的THP1单核细胞中TLR表达的增加以及X射线照射的巨噬细胞样细胞中TLR表达的降低。本研究表明，电离辐射通过JNK途径调节配体反应性TLR的表达，这取决于细胞的分化状态。
