Selective suppression of IL-12 production by chemoattractants
Selective suppression of IL-12 production by chemoattractants
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DOI：
10.4049/jimmunol.164.6.3009
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发表时间：
2000-03-15
影响因子：
4.4
通讯作者：
Kelsall, BL
中科院分区：
文献类型：
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作者：
Braun, MC;Lahey, E;Kelsall, BL
我们研究了化学引诱物影响人单核细胞和树突状细胞产生IL-12的能力。我们发现用巨噬细胞趋化蛋白预处理单核细胞（MCP-1至MCP-4）或C5 a，而不是基质衍生因子-1、巨噬细胞炎性蛋白-1 α、RANTES或嗜酸性粒细胞趋化因子，抑制响应于金黄色葡萄球菌、科万菌株1（SAC）和IFN-γ刺激的IL-12 p70产生。然而，受到任何化学引诱物的影响都很小。MCP-1 ~ MCP-4对IL-12 p70产生的抑制程度是供体依赖性的，并受IL-10自分泌抑制作用的影响。相反，C5 a以非n-10依赖性方式显著抑制IL-12产生。TGF-β 1和PGE（2）对任何测试的化学引诱物抑制IL-12都不重要。IL-12 p35和p40基因mRNA的积累被趋化因子预处理抑制。有趣的是，MCP-1至MCP-4和C5 a不抑制用CD 40配体和IFN-γ或SAC和IFN-γ刺激的单核细胞来源的树突状细胞（DC）产生IL-12，这表明这些因子可能在炎症部位起作用以抑制IL-12和IFN-γ产生，而不是在淋巴结中起作用以影响T细胞引发。尽管C5 a不能抑制DC产生IL-PZ，但这些细胞表达C5 a的受体（CD 88），并且重组C5 a诱导Ca 2+通量。总之，这些结果定义了一系列具有抑制人单核细胞产生IL-12的能力的化学引诱物分子，并对体内免疫应答的调节具有广泛的意义。
We investigated the ability of chemoattractants to affect IL-12 production by human monocytes and dendritic cells. We found that pretreatment of monocytes with macrophage chemoattractant proteins (MCP-1 to -4), or C5a, but not stromal-derived factor-1, macrophage inflammatory protein-1 alpha, RANTES, or eotaxin, inhibited IL-12 p70 production in response to stimulation with Staphylococcus aureus, Cowan strain 1 (SAC), and IFN-gamma, The production of TNF-alpha and IL-10, however, was minimally affected by any of the chemoattractants. The degree of inhibition of IL-12 p70 production by MCP-1 to -4 was donor dependent and was affected by the autocrine inhibitory effects of IL-10, In contrast, C5a profoundly suppressed IL-12 production in an n-10-independent fashion. Neither TGF-beta 1 nor PGE(2) was important for the suppression of IL-12 by any of the chemoattractants tested. The accumulation of mRNA for both IL-12 p35 and p40 genes was inhibited by chemokine pretreatment. Interestingly, MCP-1 to -4 and C5a did not suppress IL-12 production by monocyte-derived dendritic cells (DC) stimulated with CD40 ligand and IFN-gamma or by SAC and IFN-gamma, suggesting that these factors may act at the site of inflammation to suppress IL-12 and IFN-gamma production rather than in the lymph node to affect T cell priming. Despite the inability of C5a to inhibit IL-PZ production by DCs, the receptor for C5a (CD88) was expressed by these cells, and recombinant C5a induced a Ca2+ flux. Taken together, these results define a range of chemoattractant molecules with the ability to suppress IL-12 production by human monocytes and have broad implications for the regulation of immune responses in vivo.