Matsutani Takeshi, Tamura Kazuhiro, Kutsukake Masahiko, Matsuda Akihisa, Tachikawa Eiichi, Uchida Eiji
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School.
Department of Endocrine & Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences.
Biol Pharm Bull. 2017;40(5):638-644. doi: 10.1248/bpb.b16-00883.
Pioglitazone improves sepsis-induced organ injury accompanied with anti-inflammatory effects on visceral adipose tissue. However, its action in adipose immune cells remains to be ascertained. We investigated the effects of pioglitazone on visceral adipose macrophage population and polarisation in cecal ligation and puncture (CLP)-induced sepsis mice. Eight-week-old male mice were assigned to 3 groups: 1) sham-operated group, 2) CLP group, or 3) pioglitazone-treated CLP group. Pioglitazone (10 mg/kg) was injected intraperitonally for 7 d and CLP surgery was performed. Visceral adipose tissues were collected 24 h after the surgery. mRNA expression of several macrophage markers (inducible nitric oxide synthase (iNOS) for M1, arginase1 (Arg1) and interleukin (IL)-10 for M2, CD163 and F4/80 for mature macrophages) and inflammatory adipokines (IL-6, monocyte chemoattractant protein-1: MCP-1) was quantified by real-time RT-PCR. Tissue sections were subjected to the immunohistochemical analysis and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. CLP significantly enhanced Arg1, IL-10 and iNOS mRNA expressions as compared with the sham group, and pioglitazone significantly increased the mRNA level of CD163 and F4/80 in CLP mice. Expression of IL-6 and MCP-1 stimulated by CLP was reduced by pioglitazone treatment. Increased CD11b/c- and CD163-positive cells as well as apoptotic cells were observed in the CLP group and the pioglitazone-treated group. The data indicate that M1/M2 macrophage activation of visceral adipose tissues is induced in CLP-induced mice, and the function of macrophages recruited from surrounding organs may be modulated by pioglitazone treatment.
吡格列酮可改善脓毒症诱导的器官损伤，并对内脏脂肪组织具有抗炎作用。然而，其在脂肪免疫细胞中的作用仍有待确定。我们研究了吡格列酮对盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠内脏脂肪巨噬细胞群体和极化的影响。将8周龄雄性小鼠分为3组：1）假手术组，2）CLP组，或3）吡格列酮治疗的CLP组。腹腔注射吡格列酮（10mg/kg），持续7天，然后进行CLP手术。术后24小时收集内脏脂肪组织。通过实时RT-PCR定量几种巨噬细胞标志物（M1的诱导型一氧化氮合酶（iNOS）、M2的精氨酸酶1（Arg1）和白细胞介素（IL）-10、成熟巨噬细胞的CD163和F4/80）以及炎性脂肪因子（IL-6和单核细胞趋化蛋白-1：MCP-1）的mRNA表达。对组织切片进行免疫组织化学分析和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）检测。与假手术组相比，CLP显著增强了Arg1、IL-10和iNOS的mRNA表达，吡格列酮显著增加了CLP小鼠中CD163和F4/80的mRNA水平。吡格列酮治疗降低了CLP刺激的IL-6和MCP-1的表达。在CLP组和吡格列酮治疗组中观察到CD11b/c和CD163阳性细胞以及凋亡细胞增加。数据表明，CLP诱导的小鼠内脏脂肪组织中诱导了M1/M2巨噬细胞活化，吡格列酮治疗可能调节从周围器官募集的巨噬细胞的功能。
