Activation of Toll‐like receptor 9 inhibits lipopolysaccharide‐induced receptor activator of nuclear factor kappa‐ B ligand expression in rat B lymphocytes.

B lymphocytes express multiple TLRs that regulate their cytokine production.We investigated the effect of TLR4 and TLR9 activation on receptor activator of NF‐kB ligand (RANKL) expression by rat spleen B cells. Splenocytes or purified spleen B cells from Rowett rats were cultured with TLR4 ligand Escherichia coli LPS and/or TLR9 ligand CpG‐oligodeoxynucleotide (CpG‐ODN) for 2 days. RANKL mRNA expression and the percentage of RANKL‐positive B cells were increased in rat splenocytes challenged by E. coli LPS alone. The increases were less pronounced when cells were treated with both CpG‐ODN and E. coli LPS. Microarray analysis showed that expressions of multiple cyclin‐dependent kinase (CDK) pathway‐related genes were up‐regulated only in cells treated with both E. coli LPS and CpG-ODN. This study suggests that CpG‐ODN inhibits LPS‐induced RANKL expression in rat B cells via regulation of the CDK pathway.