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PACAP 和 VIP 调节 LPS 诱导的小胶质细胞激活，并在小鼠 BV2 小胶质细胞中引发不同的表型变化。

PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells.

机构信息

Laboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, Australia.

School of Medical Science, [Neuroscience] and Brain and Mind Centre, The University of Sydney, Sydney, NSW 2006, Australia.

出版信息

Int J Mol Sci. 2021 Oct 11;22(20):10947. doi: 10.3390/ijms222010947.

DOI:10.3390/ijms222010947
PMID:34681607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8535941/
Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity are not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected microglial activation, morphology and cell migration. We found that both peptides attenuated LPS-induced expression of the microglial activation markers and (### < 0.001), as well as the pro-inflammatory mediators , , and (### < 0.001). In contrast, treatment with PACAP or VIP exerted distinct effects on microglial morphology and migration. PACAP reversed LPS-induced soma enlargement and increased the percentage of small-sized, rounded cells (54.09% vs. 12.05% in LPS-treated cells), whereas VIP promoted a phenotypic shift towards cell subpopulations with mid-sized, spindle-shaped somata (48.41% vs. 31.36% in LPS-treated cells). Additionally, PACAP was more efficient than VIP in restoring LPS-induced impairment of cell migration and the expression of urokinase plasminogen activator (uPA) in BV2 cells compared with VIP. These results suggest that whilst both PACAP and VIP exert similar immunosuppressive effects in activated BV2 microglia, each peptide triggers distinctive shifts towards phenotypes of differing morphologies and with differing migration capacities.

摘要

垂体腺苷酸环化酶激活肽（PACAP）和血管活性肠肽（VIP）是两种结构相关的免疫抑制肽。然而，这些肽调节小胶质细胞活性的潜在机制尚不完全清楚。我们使用脂多糖（LPS）诱导炎症挑战，测试了 PACAP 或 VIP 是否会对小胶质细胞激活、形态和细胞迁移产生不同的影响。我们发现，这两种肽都能减弱 LPS 诱导的小胶质细胞激活标志物 和 的表达（### < 0.001），以及促炎介质 、 、 和 （### < 0.001）。相比之下，PACAP 或 VIP 的治疗对小胶质细胞形态和迁移有明显的影响。PACAP 逆转了 LPS 诱导的胞体增大，并增加了小而圆的细胞比例（54.09% vs. LPS 处理细胞中的 12.05%），而 VIP 则促进了向具有中体型、纺锤形胞体的细胞亚群的表型转变（48.41% vs. LPS 处理细胞中的 31.36%）。此外，PACAP 在恢复 LPS 诱导的 BV2 细胞迁移和尿激酶型纤溶酶原激活物（uPA）表达的损伤方面比 VIP 更有效。这些结果表明，虽然 PACAP 和 VIP 在激活的 BV2 小胶质细胞中都有相似的免疫抑制作用，但每种肽都能引发不同形态和不同迁移能力的表型的独特转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8336/8535941/7df67cf71597/ijms-22-10947-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8336/8535941/c1871a780553/ijms-22-10947-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8336/8535941/7df67cf71597/ijms-22-10947-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8336/8535941/8f89f165b4d7/ijms-22-10947-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8336/8535941/b37d38f9e213/ijms-22-10947-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8336/8535941/c1871a780553/ijms-22-10947-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8336/8535941/7df67cf71597/ijms-22-10947-g010.jpg

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