Abstract
Bradykinin (BK) has been reported to be a mediator of brain damage in acute insults. Receptors for BK have been identified on microglia, the pathologic sensors of the brain, as well as in astrocytes. Here we report that BK attenuated lipopolysaccharide (LPS)-induced release of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL1-β) from glial cells, thus acting as an anti-inflammatory mediator in the brain. This effect was mimicked by raising intracellular cAMP or stimulating the prostanoid receptors EP2 and EP4, while it was abolished by a cAMP antagonist, a prostanoid receptor antagonist, or by an inhibitor of the inducible cyclooxygenase COX-2. BK also enhanced formation of prostaglandin E2, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) in glial cells. BK reduced LPS-induced neuronal death in neuron-glia co-cultures. This was probably mediated via glial cells since it did not affect TNF-α-induced neuronal death in pure neuronal cultures. Our data imply that BK has anti-inflammatory and neuroprotective effects in the central nervous system (CNS) by modulating glial function. [J Physiol Sci. 2007;57 Suppl:S115]
