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PKC Mediates LPS-Induced IL-1β Expression and Participates in the Pro-inflammatory Effect of A2AR Under High Glutamate Concentrations in Mouse Microglia.

Abstract：

:Pathogens such as bacterial lipopolysaccharide (LPS) play an important role in promoting the production of the inflammatory cytokines interleukin-1 beta (IL-1β) and tumour necrosis factor-α (TNF-α) in response to infection or damage in microglia. However, whether different signalling pathways regulate these two inflammatory factors remains unclear. The protein kinase C (PKC) family is involved in the regulation of inflammation, and our previous research showed that the activation of the PKC pathway played a key role in the LPS-induced transformation of the adenosine A2A receptor (A2AR) from anti-inflammatory activity to pro-inflammatory activity under high glutamate concentrations. Therefore, in the current study, we investigated the role of PKC in the LPS-induced production of these inflammatory cytokines in mouse primary microglia. GF109203X, a specific PKC inhibitor, inhibited the LPS-induced expression of IL-1β messenger ribonucleic acid and intracellular protein in a dose-dependent manner. Moreover, 5 µM GF109203X prevented LPS-induced IL-1β expression but did not significantly affect LPS-induced TNF-α expression. PKC promoted IL-1β expression by regulating the activity of NF-κB but did not significantly impact the activity of ERK1/2. A2AR activation by CGS21680, an A2AR agonist, facilitated LPS-induced IL-1β expression through the PKC pathway at high glutamate concentrations but did not significantly affect LPS-induced TNF-α expression. Taken together, these results suggest a new direction for specific intervention with LPS-induced inflammatory factors in response to specific signalling pathways and provide a mechanism for A2AR targeting, especially after brain injury, to influence inflammation by interfering with A2AR.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Fu SY,Xiong RP,Peng Y,Zhang ZH,Chen X,Zhao Y,Ning YL,Yang N,Zhou YG,Li P

doi

10.1007/s11064-019-02895-1

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

2755-2764

issue

eissn

0364-3190

issn

1573-6903

pii

10.1007/s11064-019-02895-1

journal_volume

pub_type

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PKC Mediates LPS-Induced IL-1β Expression and Participates in the Pro-inflammatory Effect of A2AR Under High Glutamate Concentrations in Mouse Microglia.