A new benzenediamine derivative modulates Toll-like receptors-induced myeloid dendritic cells activation and ameliorates lupus-like syndrome in MRLlpr/lpr mice.
Modulators of the over-activation of myeloid dendritic cells (mDCs) by Toll-like receptors (TLRs) have an advantage in the treatment of systemic lupus erythematosus (SLE). This study was designed to evaluate the effects of FC-99, a novel benzenediamine derivative, on TLR-induced activation of mDCs, and to assess the efficacy of FC-99 in a murine model of SLE. In vitro, FC-99 inhibited the phenotypic (CD40 and MHC-II) and functional activation (IL-12 and CXCL10) of mDCs induced by TLR ligands. In vivo, MRLlpr/lpr mice displayed renal diseases associated with increased levels of proteinuria and immunoglobulin, which were ameliorated by FC-99. Enhanced accumulation and activation of mDCs in lymphoid organs was also impaired by FC-99. Additionally, FC-99 inhibited the activation of IκB-α and upregulated the expression of TNFα-induced protein 3 (TNFAIP3) in vitro and in vivo. These results indicate that FC-99 modulates TLR-induced activation of mDCs and ameliorates lupus-like syndrome in MRLlpr/lpr mice. This effect is closely associated with the inhibition of IκB-α and upregulation of TNFAIP3.
['Gao|Sheng|S|', 'Gong|Yongsheng|Y|', 'Ji|Jianjian|J|', 'Yuan|Linbo|L|', 'Han|Liping|L|', 'Guo|Yimin|Y|', 'Fan|Xiaofang|X|', 'Hou|Yayi|Y|', 'Hua|Chunyan|C|']
D000818:Animals D003713:Dendritic Cells D015195:Drug Design D005260:Female D005786:Gene Expression Regulation D056747:Immunomodulation D008180:Lupus Erythematosus, Systemic D051379:Mice D019463:Mice, Inbred MRL lpr D022423:Myeloid Cells D000072000:NF-KappaB Inhibitor alpha D010655:Phenylenediamines D051193:Toll-Like Receptors D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
mDCs TLRs SLE FC-99