Colon cancer cell-derived high mobility group 1/amphoterin induces growth inhibition and apoptosis in macrophages
Colon cancer cell-derived high mobility group 1/amphoterin induces growth inhibition and apoptosis in macrophages
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DOI：
10.1016/s0002-9440(10)62296-1
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发表时间：
2005-03-01
影响因子：
6
通讯作者：
Ohmori, H
中科院分区：
文献类型：
--
作者：
Kuniyasu, H;Yano, S;Ohmori, H
高迁移率族（HMGB）1/白细胞介素是一种多功能细胞因子，参与癌症的侵袭和转移以及炎症。为了研究HMGB 1/白介素对巨噬细胞的作用，检测了U937人单核细胞白血病细胞以及大鼠腹腔和人肺泡巨噬细胞。U937细胞表达低水平的HMGB 1/促性腺激素受体，晚期糖基化终产物（AGEs）的受体，而AGEs的产生在分化的佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）-U937细胞中被诱导。用分泌HMGB 1/抗肿瘤素的WiDr人结肠癌细胞的培养基处理显示U937和PMA-U937细胞的生长抑制和PMA-U937细胞的凋亡。与WiDr细胞共培养后，HMGB 1/HMGB 1正义S-寡脱氧核苷酸（ODN）可使PMA-U937细胞数量明显减少。与此相反，与暴露于HMGB 1/抗肿瘤素反义S-ODN的WiDr细胞共培养的PMAU 937细胞在数量上得以保留。PMA U937细胞经反义S-ODN处理后对WiDr培养液不敏感。重组人HMGB 1/白藜芦醇在巯基乙酸盐诱导的大鼠腹腔巨噬细胞、PMA-U937细胞和人肺泡巨噬细胞中诱导生长抑制，这种作用可通过抗HMGB 1抗体吸收而消除。HMGB 1/阿糖胞苷诱导PNU-U937细胞JNK和Rac 1磷酸化。这些结果表明，HMGBi/阿糖胞苷诱导巨噬细胞的生长抑制和凋亡，通过胞内信号通路。
High mobility group (HMGB)1/amphoterin is a multifunctional cytokine involved in invasion and metastasis of cancer and in inflammation. To investigate HMGB1/amphoterin effects on macrophages, U937 human monocytic leukemia cells and rat peritoneal and human alveolar macrophages were examined. U937 cells expressed low levels of an HMGB1/amphoterin receptor, receptor for advanced glycation end-products (RAGE), whereas RAGE production was induced in differentiated phorbol 12-myristate 13-acetate (PMA)-U937 cells. Treatment with cultured medium of HMGB1/amphoterin-secreting WiDr human colon cancer cells showed growth inhibition of both U937 and PMA-U937 cells and apoptosis in PMA-U937 cells. The number of PMA-U937 cells was markedly decreased by co-culture with WiDr cells exposed to HMGB1/amphoterin sense S-oligodeoxynucleotide (ODN) in spheroids or monolayers. in contrast, PMAU937 cells co-cultured with WiDr cells exposed to HMGB1/amphoterin anti-sense S-ODN were preserved in number. PMA-U937 cells exposed to RAGE anti-sense S-ODN were insensitive to WiDr-cultured medium. Recombinant human HMGB1/amphoterin induced growth inhibition in thioglycollate-induced rat peritoneal macrophages, PMA-U937 cells, and human alveolar macrophages, an effect that was abrogated by absorption with anti-HMGB1 antibody. Phosphorylation of JNK and Rac1 was induced in PNU-U937 cells treated with HMGB1/amphoterin. These results suggest that HMGBi/amphoterin induces growth inhibition and apoptosis in macrophages through RAGE intracellular signaling pathway.