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Liczba wyników
2011 | 71 | 1 |
Tytuł artykułu

Metformin reduces the production of toxic molecules and affects the profile of cytokines release in LPS-stimulated rat primary microglial cultures

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
The results of recent studies suggest that metformin, in addition to its application for treating of type 2 diabetes, may also have therapeutic potential for treating neuroinflammatory diseases where reactive microglia play an essential role. However, the molecular mechanisms of action by which metformin exerts its anti-inflammatory effects remain largely unknown. Activation of AMP-activated protein kinase (AMPK) constitutes the best-known mechanism of metformin action. It is also known that some of metformin biological responses are not limited to activation of AMPK but mediated by AMPK-independent mechanisms. In this study we attempt to evaluate the effects of metformin on non-stimulated and LPS-activated rat primary microglial cell cultures. Our results support the conclusion that AMPK activated by metformin is involved in the regulating the release of TNF-alpha at the early phase of secretion. Furthermore, we found that the effects of metformin on the release of TNF-alpha at the later phases of secretion, IL-1beta, IL-6, IL-10 and TGF-beta1 as well as on the expression of arginase I, iNOS, NF-kappaB p65 and PGC-1- alpha are not AMPK-dependent because the pretreatment of LPSactivated microglia with compound C (a pharmacological inhibitor of AMPK) did not reverse the effect of metformin. Considering the described properties of metformin, we suppose that the shift of microglia towards “alternative activation” may form the basis of the drug’s beneficial effects observed in animal models of neurological disorders.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
71
Numer
1
Opis fizyczny
p.150
Twórcy
autor
  • Department of Pharmacology, Medical University of Silesia, Katowice, Poland
autor
  • Department of Pharmacology, Medical University of Silesia, Katowice, Poland
autor
  • Department of Pharmacology, Medical University of Silesia, Katowice, Poland
autor
  • Department of Pharmacology, Medical University of Silesia, Katowice, Poland
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-0598cb95-60c9-4e4f-91ec-1bdf21565197
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