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.
journal_name
Inflammationjournal_title
Inflammationauthors
Wang Y,Zhang L,Wei P,Zhang H,Liu Cdoi
10.1007/s10753-014-9818-0subject
Has Abstractpub_date
2014-06-01 00:00:00pages
978-83issue
3eissn
0360-3997issn
1573-2576journal_volume
37pub_type
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