Gene interactions and pathways from curated databases and text-mining
Journal of neuroinflammation 2010, PMID: 20712904

Resveratrol differentially modulates inflammatory responses of microglia and astrocytes.

Lu, Xiaofeng; Ma, Lili; Ruan, Lingfei; Kong, Yan; Mou, Haiwei; Zhang, Zhijie; Wang, Zhijun; Wang, Ji Ming; Le, Yingying

BACKGROUND

Inflammatory responses in the CNS mediated by activated glial cells play an important role in host-defense but are also involved in the development of neurodegenerative diseases. Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect microglia and astrocyte from inflammatory insults and explored mechanisms underlying different inhibitory effects of resveratrol on microglia and astrocytes.

METHODS

A murine microglia cell line (N9), primary microglia, or astrocytes were stimulated by LPS with or without different concentrations of resveratrol. The expression and release of proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6, MCP-1) and iNOS/NO by the cells were measured by PCR/real-time PCR and ELISA, respectively. The phosphorylation of the MAP kinase superfamily was analyzed by western blotting, and activation of NF-kappaB and AP-1 was measured by luciferase reporter assay and/or electrophoretic mobility shift assay.

RESULTS

We found that LPS stimulated the expression of TNF-alpha, IL-1beta, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappaB and AP-1 were differentially involved. Resveratrol inhibited LPS-induced expression and release of TNF-alpha, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS-induced expression of IL-1beta in microglia but not astrocytes. Resveratrol had no effect on LPS-stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS-stimulated phosphorylation of JNK in astrocytes. Resveratrol inhibited LPS-induced NF-kappaB activation in both cell types, but inhibited AP-1 activation only in microglia.

CONCLUSIONS

These results suggest that murine microglia and astrocytes produce proinflammatory cytokines and NO in response to LPS in a similar pattern with some differences in signaling molecules involved, and further suggest that resveratrol exerts anti-inflammatory effects in microglia and astrocytes by inhibiting different proinflammatory cytokines and key signaling molecules.

Diseases/Pathways annotated by Medline MESH: Inflammation
Document information provided by NCBI PubMed

Text Mining Data

MCP-1 → LPS: " We found that LPS stimulated the expression of TNF-alpha, IL-1beta, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappaB and AP-1 were differentially involved "

TNF-alpha → LPS: " We found that LPS stimulated the expression of TNF-alpha , IL-1beta, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappaB and AP-1 were differentially involved "

IL-1beta → LPS: " We found that LPS stimulated the expression of TNF-alpha, IL-1beta , IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappaB and AP-1 were differentially involved "

IL-1beta → LPS: " We found that LPS stimulated the expression of TNF-alpha, IL-1beta , IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappaB and AP-1 were differentially involved "

IL-6 → LPS: " We found that LPS stimulated the expression of TNF-alpha, IL-1beta, IL-6 , MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappaB and AP-1 were differentially involved "

iNOS → LPS: " We found that LPS stimulated the expression of TNF-alpha, IL-1beta, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappaB and AP-1 were differentially involved "

MCP-1 ⊣ IL-1beta: " Resveratrol inhibited LPS induced expression and release of TNF-alpha, IL-6, MCP-1 , and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

TNF-alpha ⊣ IL-1beta: " Resveratrol inhibited LPS induced expression and release of TNF-alpha , IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

IL-1beta ⊣ IL-6: " Resveratrol inhibited LPS induced expression and release of TNF-alpha, IL-6 , MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

IL-1beta ⊣ LPS: " Resveratrol inhibited LPS induced expression and release of TNF-alpha, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

IL-1beta ⊣ iNOS/NO: " Resveratrol inhibited LPS induced expression and release of TNF-alpha, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

MCP-1 → LPS: " Resveratrol inhibited LPS induced expression and release of TNF-alpha, IL-6, MCP-1 , and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

TNF-alpha → LPS: " Resveratrol inhibited LPS induced expression and release of TNF-alpha , IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

IL-6 → LPS: " Resveratrol inhibited LPS induced expression and release of TNF-alpha, IL-6 , MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

iNOS/NO → LPS: " Resveratrol inhibited LPS induced expression and release of TNF-alpha, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS induced expression of IL-1beta in microglia but not astrocytes "

p38 → LPS: " Resveratrol had no effect on LPS stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS stimulated phosphorylation of JNK in astrocytes "

ERK1/2 → LPS: " Resveratrol had no effect on LPS stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS stimulated phosphorylation of JNK in astrocytes "

AP-1 ⊣ LPS: " Resveratrol inhibited LPS induced NF-kappaB activation in both cell types, but inhibited AP-1 activation only in microglia "

AP-1 ⊣ NF-kappaB: " Resveratrol inhibited LPS induced NF-kappaB activation in both cell types, but inhibited AP-1 activation only in microglia "

NF-kappaB → LPS: " Resveratrol inhibited LPS induced NF-kappaB activation in both cell types, but inhibited AP-1 activation only in microglia "

Manually curated Databases

No curated data.