4.6 Article

Anti-neuroinflammatory effect of curcumin on Pam3CSK4-stimulated microglial cells

Journal

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 41, Issue 1, Pages 521-530

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2017.3217

Keywords

curcumin; anti-inflammation; Toll-like receptor 2; heme oxygenase-1

Funding

  1. Research Grants of the National Natural Science Foundation of China [81401299]
  2. Key Project of Department of Education of Guangdong Province [2015KTSCX120]
  3. Shenzhen Peacock Plan [827-000129, 827-000209, 827-000107, KQTD20140630100746562]
  4. Shenzhen Research Grant [JCYJ20150324140036854, JCYJ20160422091658982]
  5. Shenzhen Science and Technology Project [20160422091658982]

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Curcumin is the main curcuminoid present in Curcuma longa and it has been previously reported to exhibit a wide range of pharmacological activities. In the present study, the inhibitory effects of curcumin on the inflammatory mediators released by Pam3CSK4-stimulated BV-2 microglial cells were investigated. The production of pro-inflammatory mediators and cytokines, including tumor necrosis factor- (TNF-) and prostaglandin E-2 (PGE(2)), were measured by enzyme-linked immunosorbent assay (ELISA). The expression of inflammatory genes, including inducible nitric oxide synthase and cyclooxygenase-2, were further investigated using reverse transcription-quantitative polymerase chain reaction. The effects of curcumin on heme oxygenase-1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), mitogen-activated protein kinase (MAPK) and nuclear factor-B (NF-B) signaling pathways were analyzed by western blotting. The results revealed that curcumin dose-dependently inhibited Pam3CSK4-induced nitric oxide, PGE(2), and TNF- secretion. Curcumin suppressed the secretion of inflammatory mediators through an increase in the expression of HO-1. Curcumin induced HO-1 transcription and translation through the Nrf2/antioxidant response element signaling pathway. Inhibitory experiments revealed that HO-1 was required for the anti-inflammatory effects of curcumin. Further mechanistic studies demonstrated that curcumin inhibited neuroinflammation by suppressing NF-B and MAPK signaling pathways in Pam3CSK4-activated microglial cells. The results of the present study suggest that curcumin may be a novel treatment for neuroinflammation-mediated neurodegenerative disorders.

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