Molecular analysis of anti-inflammatory effect of IL-10 and IL-4 on human monocytes

IL-10和IL-4对人单核细胞抗炎作用的分子分析

• 批准号: 07671213
• 负责人: OTSUKA Takeshi
• 金额: $ 0.45万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671213/
• 关键词: monocyte; macrophage; interleukin-4; interleukin-10; cyclooxygenase; JAK; STAT; signal transduction; シクロキシゲナーゼ; 炎症制御

1.IL-4 suppressed and IL-10 rather enhanced NO by mouse monocytic cell lines. Production of TNF-a or superoxide anions were suppressed by both IL-4 and IL-10, indicating that regulatory mechanism of NO production is not regulated by TNF-a production alone. Macrophage cell lines expressing human IL-4 receptor alpha chain on the cell membrane, were suppressed NO and TNF-alpha by human IL-4.2.Mouse resident (RPMf) and thioglycollate-elicited (TPMf) peritoneal macrophages released a substantial amount of NO after stimulation with LPS or a combination of LPS and IFN-g (LPS/IFN-g). Both IL-10 and IL-4 inhibitedNO production by stimulated TPMf. On the other hand, NO production by stimulated RPMf was inhibited by IL-4, but was enhanced by IL-10.3.We examined the activation of STAT molecules by using electrophoretic mobility-shift assayusing (EMSA). Using a DNA probe corresponding to a GAS-motif sequence conserved in the promoter region of cyclooxygenase (COX) -2 genes for human, mouse and rat, STAT5 was shown to be activated in human peripheral monocytes stimulated with LPS.This activation of STAT5 was neutralized partly by an antibody against GM-CSF.

1. IL-4抑制，IL-10相当通过小鼠单核细胞系增强NO。 IL-4和IL-10都抑制了TNF-A或超氧化阴离子的产生，这表明不仅产量不受TNF-A的生产来调节无生产的调节机制。 Macrophage cell lines expressing human IL-4 receptor alpha chain on the cell membrane, were suppressed NO and TNF-alpha by human IL-4.2.Mouse resident (RPMf) and thioglycollat​​e-elicited (TPMf) peritoneal macrophages released a substantial amount of NO after stimulation with LPS or a combination of LPS and IFN-g (LPS/IFN-g). IL-10和IL-4均通过刺激的TPMF抑制了NONO的生产。另一方面，IL-4抑制了刺激的RPMF的产生，但通过IL-10.3.3.我们通过使用电泳迁移率迁移测定法（EMSA）检查了Stat分子的激活。使用对应于人，小鼠和大鼠的环氧合酶（COX）-2基因的启动子区域中的气体 - 莫蒂序列的DNA探针，STAT5被证明在用LP刺激的人外围单核细胞中激活，该抗体通过对GM-CSF的抗体进行了部分中和STAT5的激活。

项目成果

Nemoto Y,Otsuka T,Nakashima H,Tanaka Y,Kuga S,Niiro H,Niho Y: "Differential effect of IL-10 on nitric oxide production by resident and elicited murine peritoneal macrophages : Its effect in comparison with IL-4." The 9th International Congress of Immunolo

Nemoto Y、Otsuka T、Nakashima H、Tanaka Y、Kuga S、Niiro H、Niho Y：“IL-10 对驻留型和诱发型小鼠腹膜巨噬细胞产生一氧化氮的不同影响：与 IL-4 相比的影响。”

Niho Y 外: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in ironocytes" Mol.Biol.Hem.(印刷中). (1997)

Niho Y 等人：“IL-10 在铁细胞中前列腺素和细胞因子交叉调节中的作用”Mol.Biol.Hem.（出版中）。

Xu LX,Kukita T,Kukita A,Otsuka T,Niho Y,Iijima T: "Interleukin 10 selectively inhibits osteoclastogenesis by inhibiting differentiation of osteoclast progenitors into preosteoclast-like cells in rat bone marrow culture system." J.Cell Physiol. 165. 624-62

Xu LX、Kukita T、Kukita A、Otsuka T、Niho Y、Iijima T：“白细胞介素 10 通过抑制大鼠骨髓培养系统中破骨细胞祖细胞分化为前破骨细胞样细胞来选择性抑制破骨细胞生成。”

Tanaka Y 外: "Effect of interleukin-10 on collagen-induced arthritis in mice" Inflamation Resarch. 45. 283-288 (1996)

Tanaka Y 等人：“白细胞介素 10 对小鼠胶原诱导的关节炎的影响”炎症研究 45. 283-288 (1996)。

Niiro H.外: "Inhibition by interleukin-10 of induable cycloxygenase expresion in lpcplyeulaid stiunlated monocytes: Its underlyirg mechanism in comparson with interlenlin-4" Blood. 85. 3736-3745 (1995)

Niiro H. 等人：“在 lpcplyeulaid 刺激的单核细胞中，白细胞介素 10 对环氧合酶表达的抑制：与白细胞介素 4 相比，其潜在机制”《血液》85. 3736-3745 (1995)。