Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2 Microglia
2015
Аутори:
Božić, IvaSavić, Danijela
Laketa, Danijela
Bjelobaba, Ivana
Milenkovic, Ivan
Peković, Sanja
Nedeljkovic, Nadezda
Lavrnja, Irena
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Microglial cells are resident immune cells of the central nervous system
(CNS), recognized as key elements in the regulation of neural
homeostasis and the response to injury and repair. As excessive
activation of microglia may lead to neurodegeneration, therapeutic
strategies targeting its inhibition were shown to improve treatment of
most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1
(thiamine) derivate exerting potentially anti-inflammatory effects.
Despite the encouraging results regarding benfotiamine potential to
alleviate diabetic microangiopathy, neuropathy and other oxidative
stress-induced pathological conditions, its activities and cellular
mechanisms during microglial activation have yet to be elucidated. In
the present study, the anti-inflammatory effects of benfotiamine were
investigated in lipopolysaccharide (LPS)-stimulated murine BV-2
microglia. We determined that benfotiamine remodels activated microglia
to acquire the shape that is characteristic of non-stimulated BV-2
cells. In addition, benfotiamine significantly decreased production of
pro-inflammatory mediators such as inducible form of nitric oxide
synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70
(Hsp70), tumor necrosis factor alpha a (TNF-alpha), interleukin-6
(IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10)
production in LPS stimulated BV-2 microglia. Moreover, benfotiamine
suppressed the phosphorylation of extracellular signal-regulated kinases
1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B
Akt/PKB. Treatment with specific inhibitors revealed that
benfotiamine-mediated suppression of NO production was via JNK1/2 and
Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and
Akt pathways. Finally, the potentially protective effect is mediated by
the suppression of translocation of nuclear factor
kappa-light-chain-enhancer of activated B cells (NF-kappa B) in the
nucleus. Therefore, benfotiamine may have therapeutic potential for
neurodegenerative diseases by inhibiting inflammatory mediators and
enhancing anti-inflammatory factor production in activated microglia.
Извор:
Plos One, 2015, 10, e0118372
DOI: 10.1371/journal.pone.0118372
ISSN: 1932-6203