FC-98 regulates TLR9-mediated of CXCL-10 expression in dendritic cells via MAPK and STAT1 signaling pathway.
Dendritic cells (DCs), as the most potent professional antigen presenting cells, play a crucial role in both innate and adaptive immune systems. Genomic bacterial DNA mimicked by unmethylated CpG motifs is discovered to possess immunostimulatory effects. CpG-DNA recognized by Toll-like receptor 9 (TLR9) on DCs arouses many immune diseases (such as cancer, viral infection, and autoimmune disorders). In this study we investigated the effects of FC-98 on CpG-induced bone marrow-derived DCs (BMDCs). The results showed that FC-98 significantly inhibited the CpG-induced BMDCs maturation and function by suppressing the expression of surface markers (CD40, CD80, CD86, and MHCII). Moreover, FC-98 downregulated the expression of C-X-C motif chemokine 10 (CXCL-10) both at the mRNA and protein level after CpG induction. Meanwhile, FC-98 markedly affected the migration of BMDCs to T cells without affecting their endocytosis capacity. Furthermore, FC-98 was confirmed to decrease CXCL-10 expression by inhibiting CpG-induced activation of MAPKs (ERK, JNK, and p38) and STAT1 signaling. Overall, these results suggested that FC-98 was a potential molecule in the treatment of CXCL-10-mediated immune diseases.
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China.
Yonghong
Y
Yang
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China ; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China.
Huan
H
Dou
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China.
Xiaoqin
X
Li
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China.
Yuxian
Y
Song
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China.
Wei
W
Gong
Institute of Functional Biomolecules, School of Life Sciences, Nanjing University, Nanjing 210093, China.
Renxiang
R
Tan
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China ; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China.
Yayi
0000-0002-1152-9132
Y
Hou
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010641:Phenotype; D010655:Phenylenediamines / Q000737:chemistry / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D013237:Stereoisomerism; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C408982:CPG-oligonucleotide; D054357:Chemokine CXCL10; C000597553:N1-((4-fluorophenyl)methyl)-4-methyl-1,2-benzenediamine; D009838:Oligodeoxyribonucleotides; D010655:Phenylenediamines; D050794:STAT1 Transcription Factor; D051217:Toll-Like Receptor 9