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Inhibition of PI3Kδ Improves Systemic Lupus in Mice

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanying excessive inflammatory responses. Phosphoinositide 3-kinase p110δ (PI3Kδ) is reported to associate with autoimmune conditions. We here aimed to determine whether selective inhibition of PI3Kδ is effective in a lupus model of BXSB mice, using the selective PI3Kδ inhibitor IC87114, which was intraperitoneally administrated to BXSB mice aged from 14 to 22 weeks. We showed that IC87114 improved renal function by decreasing the levels of proteinuria and serum creatinine, ameliorating the pathologic changes of kidneys and IgG and C3 deposition. Serum anti-autoantibody to nuclear antigen, anti-dsDNA, IL-1β, and IL-17 were markedly reduced by IC87114 therapy. Hepatic damage was also inhibited by administration of IC87114. Expression of phosphorylated AKT (p-AKT) and monocyte chemoattractant protein-1 was inhibited and mouse survival improved. In sum, PI3Kδ activation may be a critical factor for escalating autoimmune renal and hepatic damage, and its inhibition may alleviate the autoimmune damage. Our study reveals that the selective blockade of PI3Kδ is effective for mouse SLE.

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Conflict of Interest

All authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Nephrology, General Hospital of Jinan Military Command, Jinan, 250031, China

    Yanxia Wang, Lei Zhang & Ping Wei

  2. Department of Nephrology, Zouping Hospital of Traditional Chinese Medicine, Zouping, 256200, China

    Huailiang Zhang

  3. Department of Dermatology, General Hospital of Jinan Military Command, No. 25 Shifan Road, Jinan, 250031, Shandong, China

    Cuijie Liu

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  1. Yanxia Wang
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  2. Lei Zhang
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  3. Ping Wei
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  4. Huailiang Zhang
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  5. Cuijie Liu
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Correspondence to Cuijie Liu.

Additional information

Yanxia Wang and Lei Zhang contributed equally to this study.

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Wang, Y., Zhang, L., Wei, P. et al. Inhibition of PI3Kδ Improves Systemic Lupus in Mice. Inflammation 37, 978–983 (2014). https://doi.org/10.1007/s10753-014-9818-0

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  • DOI: https://doi.org/10.1007/s10753-014-9818-0

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