Cited by 179Adenosine and Purinergic SignalingNeuroinflammation and Neurodegeneration MechanismsPain Mechanisms and Treatments

P2X7‐dependent, but differentially regulated release of IL‐6, CCL2, and TNF‐α in cultured mouse microglia

Shieh, Chu‐Hsin, Heinrich, Annette, Serchov, Tsvetan, van Calker, Dietrich, Biber, Knut·2014·Glia

Abstract

ATP is an important regulator of microglia and its effects on microglial cytokine release are currently discussed as important contributors in a variety of brain diseases. We here analyzed the effects of ATP on the production of six inflammatory mediators (IL‐6, IL‐10, CCL2, IFN‐γ, TNF‐α, and IL‐12p70) in cultured mouse primary microglia. Stimulation of P2X7 receptor by ATP (1 mM) or BzATP (500 µM) evoked the mRNA expression and release of proinflammatory cytokines IL‐6, TNF‐α, and the chemokine CCL2 in WT cells but not in P2X7−/− cells. The effects of ATP and BzATP were inhibited by the nonselective P2 receptor antagonists PPADs and suramin. Various selective P2X7 receptor antagonists blocked the P2X7‐dependent release of IL‐6 and CCL2, but, surprisingly, had no effect on BzATP‐induced release of TNF‐α in microglia. Calcium measurements confirmed that P2X7 is the main purine receptor activated by BzATP in microglia and showed that all P2X7 antagonists were functional. It is also presented that pannexin‐1 hemichannel function and potential P2X4/P2X7 heterodimers are not involved in P2X7‐dependent release of IL‐6, CCL2, and TNF‐α in microglia. How P2X7‐specific antagonists only affect P2X7‐dependent IL‐6 and CCL2 release, but not TNF‐α release is at the moment unclear, but indicates that the P2X7‐dependent release of cytokines in microglia is differentially regulated. GLIA 2014;62:592–607

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Crossref · 10.1002/glia.22628

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  • P2X7 receptor activation also promotes the release of other inflammatory mediators such as IL-6, TNF-α, CCL2, CCL3, and CXCL2.

    “Moreover, P2X7 receptor activation also promotes the release of other inflammatory mediators such as IL-6, TNF-α, CCL2, CCL3, and CXCL2 [77–80].”

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Authors
Shieh, C., Heinrich, A., Serchov, T., van Calker, D., & Biber, K.
Affiliations
  • University of Freiburg (DE)
  • Faculty of Biology University of Freiburg Freiburg Germany
  • University Medical Center Groningen (NL)
Corresponding author
Biber, Knut
Venue
Glia
Publisher
Wiley
Published
2014-01-28
Volume
62
Issue
4
Pages
592-607
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
OpenAlex
W2116854644
Cited by
179
References
65
Citations by year
2026: 5 · 2025: 5 · 2024: 12 · 2023: 13 · 2022: 13 · 2021: 27 · 2020: 14 · 2019: 19 · 2018: 17 · 2017: 22 · 2016: 13 · 2015: 12 · 2014: 7
FWCI
13.65
Type
journal article
Language
en
Open access
closed
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
P2X7 receptor, microglia, ATP, BzATP, purinergic signaling, cytokine production, interleukin-6, MCP-1, TNF-α, P2X7 antagonists, inflammatory cytokines, calcium signaling, neuroinflammation
MeSH terms
Adenosine Triphosphate, Animals, Animals, Newborn, Brain, Calcium, Cell Differentiation, Cells, Cultured, Dose-Response Relationship, Drug, Mice, Inbred C57BL, Nerve Tissue Proteins, Tumor Necrosis Factor-alpha, Interleukin-6, Microglia, Connexins, Chemokine CCL2, Mice, Receptors, Purinergic P2X7, Receptors, Purinergic P2X4, Purinergic P2X Receptor Agonists, Purinergic P2X Receptor Antagonists

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