Institute of Pathology, University Hospital, Jena, Germany.
BMC Musculoskelet Disord. 2010 Apr 7;11:63. doi: 10.1186/1471-2474-11-63.
Phosphoinositide 3-kinase gamma (PI3Kgamma) has been depicted as a major regulator of inflammatory processes, including leukocyte activation and migration towards several chemokines. This study aims to explore the role of PI3Kgamma in the murine model of antigen-induced arthritis (AIA).
Development of AIA was investigated in wildtype and PI3Kgamma-deficient mice as well as in mice treated with a specific inhibitor of PI3Kgamma (AS-605240) in comparison to untreated animals. Inflammatory reactions of leukocytes, including macrophage and T cell activation, and macrophage migration, were studied in vivo and in vitro.
Genetic deletion or pharmacological inhibition of PI3Kgamma induced a marked decrease of clinical symptoms in early AIA, together with a considerably diminished macrophage migration and activation (lower production of NO, IL-1beta, IL-6). Also, macrophage and neutrophil infiltration into the knee joint were impaired in vivo. However, T cell functions, measured by cytokine production (TNFalpha, IFNgamma, IL-2, IL-4, IL-5, IL-17) in vitro and DTH reaction in vivo were not altered, and accordingly, disease developed normally at later timepoints
PI3Kgamma specifically affects phagocyte function in the AIA model but has no impact on T cell activation.
磷酸肌醇 3-激酶γ（PI3Kγ）被描述为炎症过程的主要调节剂，包括白细胞的激活和向几种趋化因子的迁移。本研究旨在探讨 PI3Kγ在抗原诱导性关节炎（AIA）小鼠模型中的作用。
在野生型和 PI3Kγ 缺陷型小鼠以及用 PI3Kγ 特异性抑制剂（AS-605240）治疗的小鼠中研究 AIA 的发展，并与未治疗的动物进行比较。研究了白细胞的炎症反应，包括巨噬细胞和 T 细胞的激活以及巨噬细胞的迁移，包括体内和体外研究。
PI3Kγ 的基因缺失或药理学抑制在早期 AIA 中引起了明显的临床症状减轻，同时巨噬细胞的迁移和激活（NO、IL-1β、IL-6 的产生减少）也显著减少。此外，体内巨噬细胞和中性粒细胞浸润也受到损害。然而，体外细胞因子产生（TNFα、IFNγ、IL-2、IL-4、IL-5、IL-17）和体内 DTH 反应测量的 T 细胞功能未受影响，因此，疾病在后期正常发展。
PI3Kγ 特异性影响 AIA 模型中吞噬细胞的功能，但对 T 细胞激活没有影响。
