Lipopolysaccharide activates the kallikrein–kinin system in mouse choroid plexus cell line ECPC4

Abstract Regulation of the kallikrein–kinin system in cerebral inflammation is still unclear. Here, we used reverse-transcription polymerase chain reaction (RT-PCR) techniques to show that lipopolysaccharide (LPS) activates the kallikrein–kinin system by enhancing liberation of bradykinin (BK), and alters mRNA levels of kallikrein–kinin system components, including high molecular weight (H-) and low molecular weight (L-) kininogens, in ECPC4 cells, a cell line of mouse choroid plexus epithelium. LPS treatment increased liberation of immunoreactive bradykinin in the supernatant of ECPC4 cells, and addition of LPS (500 ng/ml) to cultures resulted in elevation of H- and L-kininogen mRNA levels in ECPC4 cells within 24–48 h. Furthermore, LPS treatment elevated bradykinin type 2 and type 1 receptor mRNA levels within 4 h, but did not change tissue kallikrein or plasma kallikrein mRNA levels. On the other hand, expression of pro-inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 mRNA increased within 4–8 h after addition of LPS to ECPC4 cells. The addition of IL-1β and TNF-α to investigate the major mediator for kininogen expression in ECPC4 cells remarkably induced expression of H- and L-kininogen mRNAs in ECPC4 cells. These results suggest that LPS activates the kallikrein–kinin system in the choroid plexus via autocrine induction of IL-1β and TNF-α.