Pituitary Adenylate Cyclase-Activating Polypeptide Prevents Mortality Caused by Septic Peritonitis in Mice.
Pituitary Adenylate Cyclase-Activating Polypeptide Prevents Mortality Caused by Septic Peritonitis in Mice.
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DOI：
10.4049/immunohorizons.1900044
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发表时间：
2020-04-17
期刊：
影响因子：
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通讯作者：
Ichikawa, Daisuke
中科院分区：
文献类型：
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作者：
Kono, Hiroshi;Furuya, Shinji;Ichikawa, Daisuke
本研究的目的是调查垂体腺苷酸环化酶激活多肽（PACAP）是否可以预防小鼠因败血症而死亡。在盲肠结扎穿刺 (CLP) 之前或之后的指定时间点对小鼠进行 PACAP，并调查器官损伤和死亡率。 CLP 后评估血清炎症和抗炎细胞因子水平。还测量了血浆皮质酮和促肾上腺皮质激素水平。分离的组织巨噬细胞 (Mfs) 在有或没有 PACAP 的情况下孵育，并测量细胞因子的产生。在体外存在和不存在 PACAP 的情况下，研究了从 CLP 动物分离的组织 Mf 中 NF-κB 的激活。 PACAP 治疗显着预防了 CLP 后的急性肺损伤和死亡。 PACAP 治疗组和未治疗组之间的血浆内毒素水平和细菌载量没有差异。在 CLP 后，用 PACAP 治疗的动物中，用媒介物治疗的动物中血清 TNF-α 和 HMGB1 水平的升高显着减弱。此外，与媒介物组相比，PACAP治疗组的血清IL-10水平显着更高。 PACAP 存在时，离体肝 Mfs 产生的 HMGB1 和 TNF-α 受到显着抑制，而离体肝 Mfs 和间质性肺 Mfs 产生的 IL-10 显着增加。与 CLP 后的媒介物相比，用 PACAP 治疗的动物的血浆皮质酮和促肾上腺皮质激素水平显着更高。与其他组织 Mfs 相比，PACAP 在肝脏 Mfs 中显着抑制 NF-κB 的激活。 PACAP 通过 NF-kappaB 激活抑制炎症以及可能对大脑的影响，从而预防脓毒性腹膜炎引起的死亡。
The purpose of this study was to investigate whether pituitary adenylate cyclase-activating polypeptide (PACAP) prevents mortality due to sepsis in mice. Mice were given PACAP at designated time points before or after cecal ligation and puncture (CLP), and organ injury and mortality were investigated. Serum inflammatory and anti-inflammatory cytokine levels were assessed after CLP. Plasma corticosterone and adrenocorticotropic hormone levels were also measured. Isolated tissue macrophages (Mfs) were incubated with or without PACAP, and production of cytokines was measured. Activation of NF-kappaB was investigated in tissue Mfs isolated from CLP animal in the presence and absence PACAP in vitro. PACAP treatment significantly prevented acute lung injury and mortality after CLP. Plasma endotoxin levels and bacterial load were not different between PACAP-treated and nontreated groups. Increased serum TNF-alpha and HMGB1 levels in animals treated with vehicle were significantly blunted in PACAP-treated animals after CLP. Furthermore, serum IL-10 levels were significantly greater in the PACAP-treated group compared with the vehicle group. Production of HMGB1 and TNF-alpha by isolated hepatic Mfs was significantly inhibited in the presence of PACAP, whereas production of IL-10 by isolated hepatic Mfs and interstitial lung Mfs was significantly increased. Plasma corticosterone and adrenocorticotropic hormone levels were significantly greater in the animals treated with PACAP compared with vehicle after CLP. Activation of NF-kappaB was significantly inhibited by PACAP in the hepatic Mfs compared with other tissue Mfs. PACAP prevents mortality due to septic peritonitis by inhibiting inflammation via NF-kappaB activation and possible effects on the brain.