Cordycepin Inhibits Lipopolysaccharide-Induced Inflammation by the Suppression of the MAPK-IκB-NF-κB Pathways in DCs
Department of Renal Transplant, Center of Nephropathy, The First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, Shannxi, China
Meeting: 2013 American Transplant Congress
Abstract number: D1509
Background: Dendritic cells(DCs)are professional APC playing key roles in capturing, processing and presenting antigens as the most potent professional antigen presenting cells. Lipopolysaccharide (LPS) is a potent inducer of DCs maturation.The signaling pathways involved in this process are intricate, which have not been characterized.It has been accepted that MAPK-NF-ΚB signaling pathways play an important role in the maturation of DCs.As we known cordycepin (Cs) is a polyadenylation inhibitor with a large spectrum of biological activities, including anti-proliferative, pro-apoptotic and anti-inflammatory effects. Our laboratory previous studies demonstrated that Cs caused an inhibition of LPS-induced p38 MAPK-NF-ΚB activity in macrophage.Whether Cs regulates the signaling pathway and functional alteration in LPS-activated dendritic cells has not been reported.To elucidate the immunoloregulation mechanism of Cs, we isolated mouse bone marrow-derived dendritic cells (BM-DCs) and investigated the effects of Cs on the MAPK-IΚB-NF-ΚB-phenotype and function pathways in LPS-treated DCs.Methods: Using MACS-purified mice BM-DCs and cultured with RPMI-1640 supplemented with heat-inactivated FCS, penicillin, streptomycin and GM-CSF. On day 7, the non-adherent cells and loosely adherent cells were harvested, the cells labeled with bead conjugated anti-CD11c mAb were purified and then the purity of iDCs populations was identified by flow cytometry. Then plus Cs and LPS co- cultured 72h. The cells were collected to extract cytoplasma proteins, p38 MAPK, ERK1/2 and JNKl/2 activation Was detected by Westem Blot.The effect of Cs on NF-ΚB binding activity in DCs was analyzed by electrophoretic mobility shiR assay (EMSA) and the IΚB protein level in the cytoplasma was detected by Western blot.Results: Cs increased the expression of P-p38, inhibited the expression of p-JNK, but Cs had no obvious effect on the the expression of P-ERK in LPS-induced DCs. Further more, Cs inhibited NF-ΚB activity and inhibiting IΚB phosphorylation in DCs.Conclusion: Taken together, these results suggest that cordycepin suppression of NF-ΚB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a potential therapeutic approach for inflammation-associated disorders and transplantation rejection.
To cite this abstract in AMA style:
Ding C, Tian P, Jin Z, Mao T, Li Y, Tian H, Xiang H, Pan X, Ding X, Xue W. Cordycepin Inhibits Lipopolysaccharide-Induced Inflammation by the Suppression of the MAPK-IκB-NF-κB Pathways in DCs [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/cordycepin-inhibits-lipopolysaccharide-induced-inflammation-by-the-suppression-of-the-mapk-ib-nf-b-pathways-in-dcs/. Accessed October 10, 2024.« Back to 2013 American Transplant Congress