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The activation of μ‐opioid receptor potentiates LPS‐induced NF‐kB promoting an inflammatory phenotype in microglia
Author(s) -
Gessi Stefania,
Borea Pier Andrea,
Bencivenni Serena,
Fazzi Debora,
Varani Katia,
Merighi Stefania
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12313
Subject(s) - proinflammatory cytokine , microglia , tlr4 , neuroinflammation , neuroprotection , opioid , pharmacology , receptor , opioid receptor , chemistry , nf κb , microbiology and biotechnology , signal transduction , inflammation , biology , immunology , biochemistry
Increased production of proinflammatory cytokines has a prominent role in tolerance to opioids. The objectives of this study were to examine whether μ‐opioid receptor affects proinflammatory signalling through the activation of NF‐kB in microglia. The novelty of the described research is that a low dose of morphine, exerting its effects via the μ‐opioid receptor, increases the DNA‐binding activity of NF‐kB via PKCε, while a high dose of morphine triggers a nonopiate receptor response mediated by TLR4 and, interestingly, PKCε signalling. The identification of morphine as a crucial upstream regulator of PKCε‐NF‐κB signalling in microglia argues for a central role of these pathways in neuroinflammation development and progression. Therefore, the morphine‐PKCε‐NF‐κB pathway may provide novel targets to induce neuroprotective mechanisms, thereby reducing tolerance to opioids.