Multifunctional effects of bradykinin on glial cells in relation to potential anti-inflammatory effects.
Kinins have been reported to be produced and act at the site of injury and inflammation. Despite many reports that they are likely to initiate a particular cascade of inflammatory events, bradykinin (BK) has anti-inflammatory effects in the brain mediated by glial cells. In the present review, we have attempted to describe the complex responses and immediate reaction of glial cells to BK. Glial cells express BK receptors and induce Ca(2+)-dependent signal cascades. Among them, production of prostaglandin E(2) (PGE(2)), via B(1) receptors in primary cultured microglia, has a negative feedback effect on lipopolysaccharide (LPS)-induced release of tumor necrosis factor-alpha (TNF-alpha) via increasing intracellular cyclic adenosine monophosphate (cAMP). In addition, BK up-regulates the production of neurotrophic factors such as nerve growth factor (NGF) via B(2) receptors in astrocytes. These results suggest that BK may have anti-inflammatory and neuroprotective effects in the brain through multiple functions on glial cells. These observations may help to understand the paradox on the role of kinins in the central nervous system and may be useful for therapeutic strategy.
Noda
Mami
M
Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. noda@phar.kyushu-u.ac.jp
Sasaki
Kenjiro
K
Ifuku
Masataka
M
Wada
Keiji
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005911:Gliosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D009414:Nerve Growth Factors; D018002:Receptors, Bradykinin; D014409:Tumor Necrosis Factor-alpha; D001920:Bradykinin