Lipopolysaccharide activates the kallikrein-kinin system in mouse choroid plexus cell line ECPC4.
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 4h, but did not change tissue kallikrein or plasma kallikrein mRNA levels. On the other hand, expression of pro-inflammatory mediators interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and cyclooxygenase-2 mRNA increased within 4-8h after addition of LPS to ECPC4 cells. The addition of IL-1beta and TNF-alpha 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-1beta and TNF-alpha.
Takano
Masaoki
M
Department of Life Sciences Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. takano@pharm.kobegakuin.ac.jp
Satoh
Chieko
C
Kunimatsu
Naomi
N
Otani
Mieko
M
Hamada-Kanazawa
Michiko
M
Miyake
Masaharu
M
Ming
Kyongsong
K
Yayama
Katsutoshi
K
Okamoto
Hiroshi
H
D000818:Animals; D001920:Bradykinin / Q000134:cerebrospinal fluid / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000139:chemically induced / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000494:pharmacology; D007610:Kallikreins / Q000134:cerebrospinal fluid* / Q000187:drug effects / Q000235:genetics; D007705:Kinins / Q000134:cerebrospinal fluid* / Q000187:drug effects / Q000235:genetics; D008070:Lipopolysaccharides; D051379:Mice; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D007705:Kinins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018002:Receptors, Bradykinin; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D007610:Kallikreins; D001920:Bradykinin