Lipopolysaccharide injection into the cerebral ventricle evokes kininogen induction in the rat brain.
Kinins, such as bradykinin and Lys-bradykinin, are important mediators in peripheral inflammation. Although the existence of the components necessary for generating kinins has been demonstrated in the brain, a functional role of the kinin-generating system in cerebral inflammation remains to be defined. The aim of the present study was to elucidate whether inflammatory stimuli alter the mRNA levels of components for the kallikrein-kinin system, including kallikreins, kininogens and bradykinin type 2 (B(2)-) receptor in rat brain using the reverse transcription polymerase chain reaction. The intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS; 0.25 microg/animal) resulted in the elevation of T-kininogen and high-molecular-weight (H-) kininogen mRNAs in various brain regions within 24 h, prominently in the choroid plexus. The appearance of immunoreactive T-kininogen was demonstrated in the epithelium of the choroid plexus, but not in the matrix and vessels, after i.c.v. injection of LPS. The mRNA levels of kallikreins, such as tissue kallikrein, T-kininogenase and plasma kallikrein, and B(2)-receptor did not change in any brain region following i.c.v. injection of LPS. The levels of cyclooxygenase-2 mRNA in the choroid plexus were increased within 2 h after i.c.v. injection of LPS, and pretreatment with indomethacin (3 microg/animal, i.c.v.) abolished the LPS-induced elevation of T- and H-kininogen mRNAs in the choroid plexus. The i.c.v. injection of prostaglandin E(2) (100 ng/animal) also caused increases in the mRNA levels of T- and H-kininogens in various brain regions, including the choroid plexus. These results suggest that LPS stimulates the induction of kininogens in the brain, especially the choroid plexus, by stimulating the production of arachidonic metabolites such as prostaglandin E(2).
Takano
Masaoki
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University, Ikawadani-cho, Nishi-ku, Kobe 651-2180, Japan.
Horie
Masato
M
Yayama
Katsutoshi
K
Okamoto
Hiroshi
H
D000818:Animals; D015139:Blotting, Southern; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular / Q000379:methods; D007527:Isoenzymes / Q000235:genetics; D007610:Kallikreins / Q000235:genetics; D019679:Kininogen, High-Molecular-Weight / Q000235:genetics / Q000378:metabolism*; D019728:Kininogen, Low-Molecular-Weight / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D007527:Isoenzymes; D019679:Kininogen, High-Molecular-Weight; D019728:Kininogen, Low-Molecular-Weight; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007610:Kallikreins