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Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells.
PLoS One. 2012; 7(2):e32195.Plos

Abstract

BACKGROUND

Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. Although current studies indicate that resveratrol produces neuroprotection against neurological disorders, the precise mechanisms for its beneficial effects are still not fully understood. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells.

METHODOLOGY/PRINCIPAL FINDINGS

BV-2 cells were treated with resveratrol (25, 50, and 100 µM) and/or LPS (1 µg/ml). Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10), Akt, mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP-responsive element-binding protein (CREB) were measured by western blot. Resveratrol significantly attenuated the LPS-induced expression of NO, PGE2, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. Resveratrol increased PTEN, Akt and mTOR phosphorylation in a dose-dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR inhibitor, blocked the effects of resveratrol on LPS-induced microglial activation. In addition, mTOR inhibition partially abolished the inhibitory effect of resveratrol on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK).

CONCLUSION AND IMPLICATIONS

This study indicates that resveratrol inhibited LPS-induced proinflammatory enzymes and proinflammatory cytokines via down-regulation phosphorylation of NF-κB, CREB and MAPKs family in a mTOR-dependent manner. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of resveratrol.

Authors+Show Affiliations

School of Life Science, Yunnan University, Kunming, Yunnan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22363816

Citation

Zhong, Lian-Mei, et al. "Resveratrol Inhibits Inflammatory Responses Via the Mammalian Target of Rapamycin Signaling Pathway in Cultured LPS-stimulated Microglial Cells." PloS One, vol. 7, no. 2, 2012, pp. e32195.
Zhong LM, Zong Y, Sun L, et al. Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells. PLoS One. 2012;7(2):e32195.
Zhong, L. M., Zong, Y., Sun, L., Guo, J. Z., Zhang, W., He, Y., Song, R., Wang, W. M., Xiao, C. J., & Lu, D. (2012). Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells. PloS One, 7(2), e32195. https://doi.org/10.1371/journal.pone.0032195
Zhong LM, et al. Resveratrol Inhibits Inflammatory Responses Via the Mammalian Target of Rapamycin Signaling Pathway in Cultured LPS-stimulated Microglial Cells. PLoS One. 2012;7(2):e32195. PubMed PMID: 22363816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells. AU - Zhong,Lian-Mei, AU - Zong,Yi, AU - Sun,Lin, AU - Guo,Jia-Zhi, AU - Zhang,Wei, AU - He,Ying, AU - Song,Rui, AU - Wang,Wen-Min, AU - Xiao,Chun-Jie, AU - Lu,Di, Y1 - 2012/02/21/ PY - 2011/10/10/received PY - 2012/01/24/accepted PY - 2012/2/25/entrez PY - 2012/3/1/pubmed PY - 2012/6/30/medline SP - e32195 EP - e32195 JF - PloS one JO - PLoS One VL - 7 IS - 2 N2 - BACKGROUND: Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. Although current studies indicate that resveratrol produces neuroprotection against neurological disorders, the precise mechanisms for its beneficial effects are still not fully understood. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells. METHODOLOGY/PRINCIPAL FINDINGS: BV-2 cells were treated with resveratrol (25, 50, and 100 µM) and/or LPS (1 µg/ml). Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10), Akt, mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP-responsive element-binding protein (CREB) were measured by western blot. Resveratrol significantly attenuated the LPS-induced expression of NO, PGE2, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. Resveratrol increased PTEN, Akt and mTOR phosphorylation in a dose-dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR inhibitor, blocked the effects of resveratrol on LPS-induced microglial activation. In addition, mTOR inhibition partially abolished the inhibitory effect of resveratrol on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). CONCLUSION AND IMPLICATIONS: This study indicates that resveratrol inhibited LPS-induced proinflammatory enzymes and proinflammatory cytokines via down-regulation phosphorylation of NF-κB, CREB and MAPKs family in a mTOR-dependent manner. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of resveratrol. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22363816/Resveratrol_inhibits_inflammatory_responses_via_the_mammalian_target_of_rapamycin_signaling_pathway_in_cultured_LPS_stimulated_microglial_cells_ L2 - https://dx.plos.org/10.1371/journal.pone.0032195 DB - PRIME DP - Unbound Medicine ER -