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Updated: Nov 21, 2025
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
[CD11b agonist leukadherin-1 inhibits activation of TLR7 and TLR9 in mouse bone marrow-derived dendritic cells by
Weiwei Zhai1, Mengjun Zhou2, Minghui Sun2
1College of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117; Department of Clinical Laboratory, Jining NO.1 People's Hospital, Jining 272000, China.
Abstract:
Objective To study the effect of CD11b agonist leukadherin-1 (LA1) on Toll-like receptor 7 (TLR7)- and TLR9-induced activation of mouse bone marrow-derived dendritic cells (BMDCs) and its specific mechanism. Methods BMDCs were successfully induced and the concentrations of LA1 used in the study were determined by CCK-8 assay and annexin V-FITC/PI double staining. BMDCs were treated with LA1 for 2 hours followed by stimulation of TLR7 agonist R837 and TLR9 agonist CpG1826. The expression of BMDCs surface markers CD40, CD86 and MHC-II were detected by flow cytometry; IL-6, IL-12p40 and tumor necrosis factor α (TNF-α) in the cell culture supernatant were detected by ELISA; the phosphorylation of NF-κB p65 in BMDCs was detected by Western blotting. Results LA1 concentration below 20 μmol/L had no effect on the viability and apoptosis of BMDCs. LA1 pretreatment significantly inhibited R837- and CpG 1826-induced expression of CD40, CD86 and MHC-II , and the secretion of IL-6, IL-12p40 and TNF-α in BMDCs. Moreover, LA1 pretreatment significantly inhibited the phosphorylation of NF-κB p65 activated by R837 and CpG1826 in BMDCs. Conclusion CD11b agonist LA1 can significantly inhibit the activation of TLR7 and TLR9 in BMDCs by blocking the NF-κB p65 signaling pathway.
