Monocyte to macrophage differentiation-associated (MMD) positively regulates ERK and Akt activation and TNF-α and NO production in macrophages
Monocyte to macrophage differentiation-associated (MMD) positively regulates ERK and Akt activation and TNF-α and NO production in macrophages
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DOI：
10.1007/s11033-011-1370-5
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发表时间：
2012-05-01
影响因子：
2.8
通讯作者：
Han, Hua
中科院分区：
文献类型：
--
作者：
Liu, Qiang;Zheng, Jin;Han, Hua
巨噬细胞的活化受环境因素和内源性程序的调节。在本研究中，我们研究了PAQR家族蛋白--单核细胞向巨噬细胞分化相关蛋白（MMD）在巨噬细胞活化中的作用，并揭示了其潜在的分子机制。我们的研究结果表明，虽然MMD的表达可以检测到在所有组织检查，其表达水平显着上调后单核细胞分化。在细胞内，EGFP-MMD融合蛋白可共定位于内质网、线粒体、高尔基体，但不定位于溶酶体和细胞质。LPS刺激后巨噬细胞MMD表达上调，这可能受到Notch信号的关键转录因子RBP-J的调节。MMD在巨噬细胞中的过表达增加了LPS刺激后TNF-α和NO的产生。我们发现MMD过表达增强了LPS刺激后巨噬细胞ERK 1/2和Akt的磷酸化。通过药理学试剂阻断Erk或Akt分别减少MMD过表达巨噬细胞中TNF-α或NO的产生。这些结果表明，MMD调节巨噬细胞TNF-α和NO的产生，这一过程可能涉及Erk或Akt。
Macrophage activation is modulated by both environmental cues and endogenous programs. In the present study, we investigated the role of a PAQR family protein, monocyte to macrophage differentiation-associated (MMD), in macrophage activation and unveiled its underlying molecular mechanism. Our results showed that while MMD expression could be detected in all tissues examined, its expression level is significantly up-regulated upon monocyte differentiation. Within cells, EGFP-MMD fusion protein could be co-localized to endoplasmic reticulum, mitochondria, Golgi apparatus, but not lysosomes and cytoplasm. MMD expression is up-regulated in macrophages after LPS stimulation, and this might be modulated by RBP-J, the critical transcription factor of Notch signaling. Overexpression of MMD in macrophages increased the production of TNF-alpha and NO upon LPS stimulation. We found that MMD overexpression enhanced ERK1/2 and Akt phosphorylation in macrophages after LPS stimulation. Blocking Erk or Akt by pharmacological agent reduced TNF-alpha or NO production in MMD-overexpressing macrophages, respectively. These results suggested that MMD modulates TNF-alpha and NO production in macrophages, and this process might involves Erk or Akt.