Ultraviolet (UV) B irradiation of the skin induces acute inflammation, as characterized by erythema, edema, and immunosuppression, and is subsequently linked to the progression of skin cancer. Toll‐like receptor 4 (TLR4), a component of innate immunity, has been shown to play an important role in cancer. To elucidate the role of TLR4 in UVB‐induced tumor development, TLR4‐proficient (C3H/HeN) and TLR4‐deficient (C3H/HeJ) mice were exposed to multiple doses of UVB radiation (200 mJ/cm²) for 40 weeks. Photocarcinogenesis was retarded in terms of tumor incidence, and tumor latency, in mice deficient in TLR4 compared with TLR4‐proficient mice, whereas significantly greater numbers of tumors occurred in TLR4‐proficient mice. There was significant upregulation of inflammatory markers like COX‐2, PGE₂, S100A8, and S100A9 in the skin of TLR4‐proficient mice than the skin of TLR4‐deficient mice. Furthermore, we found that TLR4‐proficient mice had a significantly higher number of Gr1+CD11b+ myeloid cells CD4+CD25+ regulatory T‐cells than TLR4‐deficient mice. Furthermore, the levels of interferon (IFN)‐γ cytokine was increased and the levels of interleukin (IL)‐4, IL‐10, and IL‐17 cytokines were decreased in serum, skin, and tumor lysates of TLR4‐deficient mice in comparison with samples from TLR4‐proficient mice. Together, our data indicate that TLR4‐mediated inflammation may cause suppression of antitumor responses and trigger the development of UVB‐induced skin cancers. Thus, strategies to inhibit TLR4‐mediated immune suppression may allow us to develop preventive and therapeutic approaches for the management of UVB‐induced cutaneous tumors.

中文翻译：

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Toll样受体4缺乏症通过调节免疫和炎症反应来抑制紫外线诱导的肿瘤发展

皮肤的紫外线（UV）B辐射会诱发急性炎症，其特征是红斑，水肿和免疫抑制，并随后与皮肤癌的进展有关。Toll样受体4（TLR4）是先天免疫的组成部分，已显示在癌症中起重要作用。为了阐明TLR4在UVB诱导的肿瘤发生中的作用，将TLR4熟练（C3H / HeN）和TLR4缺乏（C3H / HeJ）小鼠暴露于多次剂量的UVB辐射（200 mJ / cm ²）中40周。与TLR4熟练的小鼠相比，TLR4缺乏的小鼠的光致癌作用在肿瘤发生率和潜伏期方面均受到抑制，而在TLR4熟练的小鼠中发生的肿瘤数量要多得多。炎症标记物（例如COX-2，PGE ₂）显着上调，比TLR4缺陷小鼠的皮肤中的S100A8和S100A9更高。此外，我们发现，与TLR4缺陷小鼠相比，具有TLR4缺陷的小鼠的Gr1 + CD11b +髓样细胞CD4 + CD25 +调节性T细胞的数量明显更高。此外，TLR4缺陷小鼠的血清，皮肤和肿瘤裂解物中的干扰素（IFN）-γ细胞因子水平升高，白介素（IL）-4，IL-10和IL-17细胞因子水平降低。与TLR4精通小鼠的样品进行比较。总之，我们的数据表明TLR4介导的炎症可能会导致抗肿瘤反应的抑制并引发UVB诱导的皮肤癌的发展。因此，抑制TLR4介导的免疫抑制的策略可能使我们能够开发预防性和治疗性方法来管理UVB诱导的皮肤肿瘤。