Research article
Loss of phosphoinositide 3-kinase γ decreases migration and activation of phagocytes but not T cell activation in antigen-induced arthritis
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* Corresponding author: Rolf Bräuer Rolf.Braeuer@med.uni-jena.de
- † Equal contributors
1 Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich Schiller University, Jena, Germany
2 Institute of Pathology, University Hospital, Jena, Germany
BMC Musculoskeletal Disorders 2010, 11:63 doi:10.1186/1471-2474-11-63
Published: 7 April 2010Abstract
Background
Phosphoinositide 3-kinase γ (PI3Kγ) 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 PI3Kγ in the murine model of antigen-induced arthritis (AIA).
Methods
Development of AIA was investigated in wildtype and PI3Kγ-deficient mice as well as in mice treated with a specific inhibitor of PI3Kγ (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.
Results
Genetic deletion or pharmacological inhibition of PI3Kγ induced a marked decrease of clinical symptoms in early AIA, together with a considerably diminished macrophage migration and activation (lower production of NO, IL-1β, IL-6). Also, macrophage and neutrophil infiltration into the knee joint were impaired in vivo. However, T cell functions, measured by cytokine production (TNFα, IFNγ, 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
Conclusion
PI3Kγ specifically affects phagocyte function in the AIA model but has no impact on T cell activation.