Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation of immune-inflammatory diseases.
Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation of immune-inflammatory diseases.
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DOI：
10.1186/ar2074
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发表时间：
2006
影响因子：
4.9
通讯作者：
Yamamoto, Kazuhiko
中科院分区：
文献类型：
--
作者：
Shoda, Hirofumi;Fujio, Keishi;Yamaguchi, Yumi;Okamoto, Akiko;Sawada, Tetsuji;Kochi, Yuta;Yamamoto, Kazuhiko
IL-32是新近在人类体内发现的一种细胞因子，可在体外诱导肿瘤坏死因子α(α)。我们研究了IL-32与肿瘤坏死因子α的体内关系，以及IL-32在肿瘤坏死因子α相关疾病-关节炎和结肠炎中的病理作用。定量聚合酶链式反应证实IL-32mRNA在淋巴组织中表达，在刺激后的外周T细胞、单核细胞和B细胞中表达。活化的T细胞对单核细胞和B细胞中IL-32mRNA的表达起重要作用。有趣的是，肿瘤坏死因子α可相互诱导T细胞、单核细胞来源的树突状细胞和滑膜成纤维细胞表达IL-32mRNA。此外，原位杂交显示IL-32mRNA在类风湿关节炎患者滑膜组织中显著表达，尤其在滑膜浸润性淋巴细胞中表达更明显。为了探讨IL-32与肿瘤坏死因子α的体内关系，我们通过骨髓移植制备了人IL-32β过表达模型小鼠(BM-IL-32)。BM-hIL-32小鼠脾细胞表达和分泌肿瘤坏死因子α、IL-1β和IL-6增加，尤以内毒素刺激为甚。此外，BM-hIL-32小鼠血清肿瘤坏死因子α浓度明显升高。脾细胞分选结果显示，静息状态下F4/80+巨噬细胞表达肿瘤坏死因子α，内毒素刺激的F4/80+巨噬细胞和树突状细胞表达IL-1α、IL-1β和IL-6。事实上，BM-HIL-32小鼠表现出胶原抗体诱导的关节炎和三硝基苯磺酸诱导的结肠炎的恶化。此外，产生hIL-32CD4+T细胞的转移显著加重了胶原诱导的关节炎，而肿瘤坏死因子α阻断则取消了hIL-32β的加重作用。因此，我们得出结论：IL-32与肿瘤坏死因子α密切相关，并在肿瘤坏死因子α相关性炎性关节炎和结肠炎的加重中起作用。
IL-32 is a newly described cytokine in the human found to be an in vitro inducer of tumor necrosis factor alpha (TNFα). We examined the in vivo relationship between IL-32 and TNFα, and the pathologic role of IL-32 in the TNFα-related diseases – arthritis and colitis. We demonstrated by quantitative PCR assay that IL-32 mRNA was expressed in the lymphoid tissues, and in stimulated peripheral T cells, monocytes, and B cells. Activated T cells were important for IL-32 mRNA expression in monocytes and B cells. Interestingly, TNFα reciprocally induced IL-32 mRNA expression in T cells, monocyte-derived dendritic cells, and synovial fibroblasts. Moreover, IL-32 mRNA expression was prominent in the synovial tissues of rheumatoid arthritis patients, especially in synovial-infiltrated lymphocytes by in situ hybridization. To examine the in vivo relationship of IL-32 and TNFα, we prepared an overexpression model mouse of human IL-32β (BM-hIL-32) by bone marrow transplantation. Splenocytes of BM-hIL-32 mice showed increased expression and secretion of TNFα, IL-1β, and IL-6 especially in response to lipopolysaccharide stimulation. Moreover, serum TNFα concentration showed a clear increase in BM-hIL-32 mice. Cell-sorting analysis of splenocytes showed that the expression of TNFα was increased in resting F4/80+ macrophages, and the expression of TNFα, IL-1β and IL-6 was increased in lipopolysaccharide-stimulated F4/80+ macrophages and CD11c+ dendritic cells. In fact, BM-hIL-32 mice showed exacerbation of collagen-antibody-induced arthritis and trinitrobenzen sulfonic acid-induced colitis. In addition, the transfer of hIL-32β-producing CD4+ T cells significantly exacerbated collagen-induced arthritis, and a TNFα blockade cancelled the exacerbating effects of hIL-32β. We therefore conclude that IL-32 is closely associated with TNFα, and contributes to the exacerbation of TNFα-related inflammatory arthritis and colitis.