ReferenceID 5577

Ascorbic acid along with ciprofloxacin regulates S. aureus induced microglial inflammatory responses and oxidative stress through TLR-2 and glucocorticoid receptor modulation

Inflammopharmacology

Microglial inflammatory responses play a central role in the pathogenesis of S. aureus induced brain infections. Upon activation, microglia produces free radicals (ROS/RNS) and disrupts the cellular antioxidant defense t

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Reference Id
5577
Evidence Id
22167
Core Evidence Id
22167
Source Reference Id
4374
Herb2 Reference Id
HBREF005171
Subject Paper Key
HBIN032689_35704229
Pubmed Id
35704229
Doi
10.1007/s10787-022-01012-z
Paper Title
Ascorbic acid along with ciprofloxacin regulates S. aureus induced microglial inflammatory responses and oxidative stress through TLR-2 and glucocorticoid receptor modulation
Paper Abstract
Microglial inflammatory responses play a central role in the pathogenesis of S. aureus induced brain infections. Upon activation, microglia produces free radicals (ROS/RNS) and disrupts the cellular antioxidant defense to combat invading microorganisms. Despite conventional antibiotic or steroid therapy, microglial over-activation could not be controlled. So, an attempt had been taken by using a natural antioxidant ascorbic acid along with ciprofloxacin to regulate microglial over-activation by involving TLR-2 and glucocorticoid receptor (GR) in an in-vitro cell culture-based study. Combinatorial treatment during TLR-2 neutralization effectively reduced the bacterial burden at 60 min compared to the GR blocking condition (p < 0.05). Moreover, the infection-induced H 2 O 2 , O 2 .- , and NO release in microglial cell culture was diminished possibly by enhancing SOD and catalase activities in the same condition (p < 0.05). The arginase activity was markedly increased after TLR-2 blocking in the combinatorial group compared to single treatments (p < 0.05). Experimental results indicated that combinatorial treatment may act through up-regulating GR expression by augmenting endogenous corticosterone levels. However, better bacterial clearance could further suppress the TLR-2 mediated pro-inflammatory NF-κB signaling. From Western blot analysis, it was concluded that ciprofloxacin-ascorbic acid combination in presence of anti-TLR-2 antibody exhibited 81.25% inhibition of TLR-2 expression while the inhibition for GR was 3.57% with respect to the infected group. Therefore, during TLR-2 blockade ascorbic acid combination might be responsible for the restoration of redox balance in microglia via modulating TLR-2/GR interaction. The combination treatment could play a major role in the neuroendocrine-immune regulation of S. aureus induced microglial activation.
Journal
Inflammopharmacology
Publish Year
2022
Experiment Subject
microglial cell culture
Experiment Type
Cell Experiment
Phenotype Related
S. Aureus; Brain Infections
Paper Title Cn
Paper Title En
Ascorbic acid along with ciprofloxacin regulates S. aureus induced microglial inflammatory responses and oxidative stress through TLR-2 and glucocorticoid receptor modulation
Bilingual Status
semi_complete