Human astrocytic bradykinin B2 receptor modulates zymosan-induced cytokine expression in 1321N1 cells

Bradykinin is an important modulator of the neurons and glial cells of the nervous system. Bradykinin secreted from neurons affects astrocytic functions such as neurovascular coupling and astrocytic cytokine production. In human astrocytes, however, the detailed mechanism of bradykinin-mediated modulation of astrocytic functions has not yet been fully elucidated. Here, we report the functional expression of the bradykinin B2 receptor and its modulation of zymosan-induced cytokine expression in human astrocytoma 1321N1 cells. Bradykinin increased cytosolic [Ca2+] in a concentration-dependent manner, whereas [des-Arg10] kallidin (an agonist of the B1 receptor) did not have this effect. Bradykinin also triggered intracellular InsP3 production. Pretreating the cells with HOE140 (icatibant acetate, a B2 receptor antagonist) inhibited the bradykinin-induced increase in cytosolic [Ca2+] and InsP3 production. In contrast, [des-Arg10]HOE140 (a B1 receptor antagonist) did not show any inhibitory effect. Bradykinin increased the zymosan-induced expression of TNF-α, and interleukin 1β (IL-1β) but did not affect the expression of interleukin 6 (IL-6) or interleukin 10 (IL-10). Interestingly, a cyclooxygenase-2 specific inhibitor blocked the bradykinin-induced effect. In contrast to the result in human glioma cells, bradykinin inhibits the zymosan-induced expression of TNF-α and IL-1β in rat astrocytes, which shows a species-dependent manner. These data suggest that bradykinin B2 receptors are expressed in human astrocytoma cells and that they modulate the expression pattern of inflammatory cytokines.