Cytokines and chemokines are both expressed by human myoblasts: possible relevance for the immune pathogenesis of muscle inflammation.
Cytokines and chemokines are both expressed by human myoblasts: possible relevance for the immune pathogenesis of muscle inflammation.
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DOI：
10.1093/intimm/12.9.1329
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Mantegazza, R
中科院分区：
文献类型：
--
作者：
De Rossi, M;Bernasconi, P;Mantegazza, R
特发性炎性肌病的特征在于针对未知肌肉组织抗原的抗体或细胞介导的免疫应答。在这些疾病中，由T和B淋巴细胞、巨噬细胞和NK细胞组成的细胞浸润可以以从血管周围间隙到肌内膜隔室的梯度侵入肌肉组织。肌细胞可能积极参与单核细胞从血流到炎症区域的募集和激活过程。为了验证该假设，在促炎细胞因子IFN-γ和TNF-α单独或组合存在的情况下，测试培养的人成肌细胞在mRNA水平和蛋白质分泌上表达不同促炎细胞因子[IL-1 α、IL-1 β、IL-6和肿瘤坏死因子（TNF）-α]和趋化因子（IL-8、MCP-1和RANTES）的能力。我们证实了人成肌细胞组成型表达IL-1 α和IL-6，而IL-1 β和TNF-α仅在用促炎细胞因子处理后检测到;此外，我们观察到成肌细胞以自分泌方式表达TNF-α，IL-8和RANTES组成型表达，而MCP-1在适当诱导后表达。这些分子数据通过培养成肌细胞上清液中的特异性ELISA进一步证实，我们的结果强调了人成肌细胞在从血流中招募白细胞中的重要性，并且最有可能的是，在浸润的炎性细胞和肌细胞之间的串扰中，为慢性炎症创造条件。此外，必须记住肌肉细胞作为免疫系统细胞的能力，也考虑到i，m。疫苗接种和分子工程化成肌细胞作为载体在基因治疗中的用途。
The idiopathic inflammatory myopathies are characterized by antibody- or cell-mediated immune response against unknown muscle tissue antigens, In these diseases a cellular infiltrate, composed of T and B lymphocytes, macrophages and NK cells, may invade muscle tissue with a gradient from the perivascular space to the endomysial compartment. Muscle cells may be actively involved in the processes of mononuclear cell recruitment and activation from the blood stream to the areas of inflammation. In order to verify this hypothesis, cultured human myoblasts were tested for their capacity to express different pro-inflammatory cytokines [IL-1 alpha, IL-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha] and chemokines (IL-8, MCP-1 and RANTES) at the mRNA level and protein secretion, in the presence of the pro-inflammatory cytokines IFN-gamma and TNF-alpha alone or in combination. We confirmed that human myoblasts expressed IL-1 alpha and IL-6 constitutively, while IL-1 beta and TNF-alpha are detected only after treatment with pro-inflammatory cytokines; moreover, we observed that TNF-alpha was expressed on an autocrine fashion by myoblasts, IL-8 and RANTES were expressed constitutively while MCP-1 after proper induction. These molecular data were further confirmed by specific ELISA in the supernatant from cultured myoblasts, Our results underline the importance of human myoblasts in the recruitment of leukocytes from the blood stream and, most probably, in the cross-talk between infiltrating inflammatory cells and muscle cells, creating the conditions for a chronic inflammation. Moreover, the capacity of muscle cells to behave as cells of the immune system has to be kept in mind, also in view of i,m. vaccination and use of molecular engineered myoblasts as vehicles in gene therapy.