Activation of Toll­like receptor 9 inhibits lipopolysaccharide­induced receptor activator of nuclear factor kappa­ B ligand expression in rat B lymphocytes.

ABSTRACT

B lymphocytes express multiple TLRs that regulate their cytokine production.We investigated the effect of TLR4 and TLR9 activation on receptor activator of NF­kB 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 CpG­oligodeoxynucleotide (CpG­ODN) for 2 days. RANKL mRNA expression and the percentage of RANKL­positive B cells were increased in rat splenocytes challenged by E. coli LPS alone. The increases were less pronounced when cells were treated with both CpG­ODN and E. coli LPS. Microarray analysis showed that expressions of multiple cyclin­dependent kinase (CDK) pathway­related genes were up­regulated only in cells treated with both E. coli LPS and CpG-ODN. This study suggests that CpG­ODN inhibits LPS­induced RANKL expression in rat B cells via regulation of the CDK pathway.