Lipopolysaccharide activation of murine splenocytes and splenic B cells increased the expression of aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator

These studies characterized the profile of AhR and ARNT expression in prima ry splenocytes and purified splenic B cells after cellular activation with lipopolysaccharide (LPS). LPS treatment of mouse splenocytes markedly incre ased the magnitude of both AhR and ARNT steady state mRNA expression, AhR m RNA expression peaked at 8 hr post-LPS activation and was increased by simi lar to 5-fold compared with freshly isolated splenocytes (i.e., time 0). AR NT mRNA expression began to increase at 8 hr postactivation, peaked at appr oximately 48 hr and was increased by approximately 4-fold when compared wit h nonactivated splenocytes at time 0. Western blotting also demonstrated an increase in the relative magnitude of both the AhR and ARNT proteins in LP S activated splenocytes. Likewise, the presence of the AhR, ARNT and cytoch rome P450lA1 (CYP1A1) proteins were also detected in purified primary splen ic B cells, and the magnitude of protein expression was enhanced in LPS act ivated splenic B cells at 12 and24 hr relative to time matched controls for each of these proteins. In summary, these findings suggest that on LPS act ivation the magnitude of AhR and ARNT mRNA and protein increases in both sp lenocytes and purified primary splenic B cells. Moreover, because the incre ase in the relative magnitude of CYP1A1 protein in response to LPS occurred in the absence of exogenous AhR ligand, these results suggest that B-cell activation is sufficient to induce AhR nuclear translocation and binding to dioxin-responsive elements in the promoter region of AhR-responsive genes.