α‐MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line
α‐MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line
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人单核细胞/巨噬细胞系中 α-MSH 的产生、受体及其对新蝶呤的影响
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
J. M. Lipton
中科院分区：
文献类型：
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作者：
N. Rajora;G. Ceriani;A. Catania;R. Star;M. Murphy;J. M. Lipton
α-促黑素细胞激素（α-MSH）是一种衍生自阿黑皮素原的十三肽，在实验动物中具有强效的促黑素活性。α-MSH抑制小鼠巨噬细胞产生一氧化氮，这种影响被认为反映了这些细胞中自分泌回路的激活，该回路基于α-MSH的产生和释放以及随后对黑皮质素受体的刺激。我们发现THP-1细胞（人类单核细胞）产生α-MSH;白细胞介素-6、肿瘤坏死因子α或伴刀豆球蛋白A可以增加这种产生。这些细胞还表达人α-MSH受体MC 1的基因。与小鼠巨噬细胞不同，THP-1细胞对干扰素-γ（IFN-γ）和脂多糖产生很少的亚硝酸盐，而a-MSH仅轻微抑制这种产生。然而，在用IFN-γ加TNF-α刺激的THP-1细胞中，新蝶呤（一种假定的灵长类动物一氧化氮同系物）的产生增加，α-MSH显著抑制了这种产生。证据表明，人单核细胞/巨噬细胞中存在基于α-MSH的自分泌调节回路，与鼠巨噬细胞中的情况非常相似。α-MSH诱导的特异性炎症介质/细胞毒性药物的调节似乎因介质在不同种属的骨髓单核细胞中的重要性而异。
α‐Melanocyte‐stimulating hormone (α‐MSH), a tridecapeptide derived from pro‐opiomelanocortin, has potent antiinflammatory activity in laboratory animals. α‐MSH inhibits nitric oxide production by murine macrophages, an influence believed to reflect activation of an autocrine circuit in these cells, one that is based on production and release of α‐MSH and subsequent stimulation of melanocortin receptors. We found that THP‐1 cells, human monocytic cells, produced α‐MSH; this production was increased by interleukin‐6, tumor necrosis factor α, or concanavalin A. These cells also expressed the gene for the human α‐MSH receptor MC1. Unlike murine macrophages, THP‐1 cells produced little nitrite in response to interferon‐γ(IFN‐γ) and lipopolysaccharide, and a‐MSH inhibited this production only slightly. However, production of neopterin, a presumed primate homologue of nitric oxide in lower animals, was increased in THP‐1 cells stimulated with IFN‐γ plus TNF‐α and α‐MSH significantly inhibited this production. The evidence indicates that an autocrine regulatory circuit based on α‐MSH occurs in human monocyte/macrophages much as in murine macrophages. α‐MSH‐induced modulation of specific inflammatory mediators/cytotoxic agents appears to differ depending on the importance of the mediators in the myelomonocytic cells of different species.