Involvement of the cAMP-dependent signal transduction pathways in the mucosal adjuvant activity by bacterial diarrheal toxin

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In order to analyze the involvement of cAMP in mucosal adjuvant activity induced by cholera toxin (CT) in molecular biological level, various assays were employed by using the CT, its mutant CT(E112Q) and the B subunit (CTB). The CT bound to the splenocytes through the interaction between CTB and GM1, followed by the activation of the PKA-CREB pathway which was downstream signal of cAMP and p38-CREB pathways, dependent on the enzymatic activity of the A subunit. Furthermore, the splenocytes, which were prepared from mice which were administered intranasally with the CT, produced cytokines in response to the stimulation from the CT and E112Q. These activities were neither found in the splenocytes nor the mice treated with E112Q and CTB, indicating that the cAMP-dependent signal transduction induced by the activity of the CT involves some adjuvant activities.