Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB- but not chemically induced non-melanoma skin cancer.
Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB- but not chemically induced non-melanoma skin cancer.
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DOI：
10.1038/s41598-023-38748-9
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发表时间：
2023-07-18
影响因子：
4.6
通讯作者：
Baron, Jens Malte
中科院分区：
文献类型：
--
作者：
Huth, Sebastian;Huth, Laura;Heise, Ruth;Marquardt, Yvonne;Lopopolo, Linda;Piecychna, Marta;Boor, Peter;Fingerle-Rowson, Guenter;Kapurniotu, Aphrodite;Yazdi, Amir S.;Bucala, Richard;Bernhagen, Juergen;Baron, Jens Malte
非黑色素瘤皮肤癌（NMSC）是全世界白人中最常见的癌症。我们研究了MIF及其同系物D-DT在UVB和化学诱导的NMSC中的病理生理作用，使用无毛SKH 1背景下的Mif−/−、D-dt−/−和Mif−/−/D-dt−/−小鼠。两种细胞因子的敲除对急性UVB照射后的炎症和慢性UVB照射期间的肿瘤形成显示出类似的减弱作用，而在双敲除小鼠中没有注意到相加的保护作用，这表明两种细胞因子激活类似的信号传导阈值。相比之下，Mif和D-dt的基因缺失对化学诱导的皮肤肿瘤没有重大影响。为了深入了解其作用机制，我们使用了含有巨噬细胞的体外3D皮肤模型。应用重组MIF和D-DT导致表皮部分内巨噬细胞的积累，这可以通过选择性MIF和D-DT途径抑制剂逆转。总之，我们的数据表明，MIF和D-DT有助于UVB的发展和进展，但不是化学诱导的NMSC，这两种细胞因子对表皮巨噬细胞积累的作用至少部分地解释了这一作用。这些数据强调，MIF和D-DT都是潜在的治疗靶点，用于预防光致癌作用，而不是化学致癌作用。
Non-melanoma skin cancer (NMSC) is the most common cancer in Caucasians worldwide. We investigated the pathophysiological role of MIF and its homolog D-DT in UVB- and chemically induced NMSC using Mif−/−, D-dt−/− and Mif−/−/D-dt−/− mice on a hairless SKH1 background. Knockout of both cytokines showed similar attenuating effects on inflammation after acute UVB irradiation and tumor formation during chronic UVB irradiation, without additive protective effects noted in double knockout mice, indicating that both cytokines activate a similar signaling threshold. In contrast, genetic deletion of Mif and D-dt had no major effects on chemically induced skin tumors. To get insight into the contributing mechanisms, we used an in vitro 3D skin model with incorporated macrophages. Application of recombinant MIF and D-DT led to an accumulation of macrophages within the epidermal part that could be reversed by selective inhibitors of MIF and D-DT pathways. In summary, our data indicate that MIF and D-DT contribute to the development and progression of UVB- but not chemically induced NMSC, a role at least partially accounted by effects of both cytokines on epidermal macrophage accumulation. These data highlight that MIF and D-DT are both potential therapeutic targets for the prevention of photocarcinogenesis but not chemical carcinogenesis.
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DOI：
10.4049/jimmunol.181.4.2330
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Coleman AM;Rendon BE;Zhao M;Qian MW;Bucala R;Xin D;Mitchell RA
通讯作者：
Mitchell RA
影响因子：
3.7
作者：
Kim, Hyunmi;Casta, Alexandre;Christiano, Angela M.
通讯作者：
Christiano, Angela M.
影响因子：
20.3
作者：
Eash, Kyle J.;Means, Jacquelyn M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
32.4
作者：
Bucala, Richard;Donnelly, Seamas C.
通讯作者：
Donnelly, Seamas C.
影响因子：
4.8
作者：
Kim, Bong-Sung;Tilstam, Pathricia V.;Bucala, Richard
通讯作者：
Bucala, Richard