Neuronal injury induces microglial production of macrophage inflammatory protein‐1α in rat corticostriatal slice cultures

Okamura, Toshiyuki; Katayama, Takahiro; Obinata, Chihiro; Iso, Yukina; Chiba, Yuzuho; Kobayashi, H; Yamada, Yuma; Harashima, Hideyoshi; Minami, Masabumi

doi:10.1002/jnr.23105

Cited by 13 publications

(15 citation statements)

References 26 publications

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“…Microglia have been shown to express CCL3 upon activation and CCL3 expression in the spinal cord has been correlated with the development of pain . Additionally, increases in Iba1+ microglia at the site of injury and microglia‐specific expression of CCL3 is linked to the development of persistent inflammation .…”

Section: Resultsmentioning

confidence: 99%

Experimental autoimmune prostatitis induces microglial activation in the spinal cord

et al. 2014

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Background The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host’s immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Methods Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S4–S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Results Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Conclusion Our data shows that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain.

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Section: Resultsmentioning

confidence: 99%

Experimental autoimmune prostatitis induces microglial activation in the spinal cord

et al. 2014

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“…CCL3 is involved in acute inflammatory responses in brain and its gene expression increases after neuronal injury (Okamura et al . ). RBM45 is reported to accumulate in inclusion bodies in neurons of amyotrophic lateral syndrome (ALS) patients.…”

Section: Discussionmentioning

confidence: 97%

Nrf2 deficiency leads to behavioral, neurochemical and transcriptional changes in mice

et al. 2013

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Nrf2 is a transcription factor that regulates the antioxidant and detoxification enzyme genes and provides defense against oxidative and electrophilic stresses in various tissues. In brain, while neuroprotective functions of Nrf2 have been well documented, Nrf2 contribution to the brain function remains to be elucidated. To address this issue, we investigated whether Nrf2 deficiency affects psychological behaviors, neurotransmitter systems and gene expressions in mice. We conducted four behavioral tests, social interaction, open-field, rotarod and forced swimming tests and found that Nrf2 knockout mice exhibited reduced immobility in the forced swimming test. Neurochemical analyses revealed that the dopamine and serotonin metabolites increased in the brains of Nrf2 knockout mice. We also present a catalog of genes whose expression is Nrf2-dependent in brain under unstressed conditions, which includes a number of xenobiotic-metabolizing enzyme genes. These results thus support our contention that Nrf2 regulates its target genes in brain under unstressed conditions and loss of Nrf2 affects various brain functions.

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“…Resting BV-2 cells also exhibited a high baseline expression of three major chemokines ; MIP-1α (CCL3) > MIP-1g (CCL9) > and MCP-I (CCL2) all of which are elevated in CNS disease, trauma (Kochanek et al, 2013, Rhodes et al, 2009), excitotoxic neurodegeneration (Okamura et al, 2012), MPTP damage to dopaminergic neurons (Kalkonde et al, 2007) and in patients with Alzheimer’s disease (Liao, Guan, 2011). In AD models, MIP-1α can activate astrocytes and microligal cells associated with Abeta (1–40) damage to the hippocampus, suggesting a primary role in neurodegeneration (Passos et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

Taka

Mazzio

Goodman

et al. 2015

Journal of Neuroimmunology

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Thymoquinone (TQ), the main pharmacological active ingredient within the black cumin seed (Nigella sativa) is believed to be responsible for therapeutic effects on chronic inflammatory conditions such as arthritis, asthma and neurodegeneration. In this study, we evaluated the potential anti-inflammatory role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. The results obtained indicated that TQ was effective in reducing NO2- with an IC50 of 5.04 μM, relative to selective iNOS inhibitor LNIL- L-N6-(1-Iminoethyl)lysine (IC50 4.09 μM). TQ mediated reduction in NO2- was found to parallel the decline of iNOS protein expression as confirmed by immunocytochemistry. In the next study, we evaluated the anti-inflammatory effects of TQ on ninety – six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody protein array. Data obtained establish a baseline protein expression profile characteristic of resting BV-2 cells in the order of osteopontin > MIP-1alpha > MIP-1g > IGF-1 and MCP-I. In the presence of LPS [1ug/ml], activated BV-2 cells produced a sharp rise in specific pro-inflammatory cytokines/chemokine’s IL-6, IL-12p40/70, CCL12 /MCP-5, CCL2 / MCP-1, and G-CSF which were attenuated by the addition of TQ (10μM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6 protein in supernatants from activated BV-2 cells were corroborated by independent ELISA and mRNA expression profiling using RT2 Profiler PCR cytokine arrays. Moreover, the data obtained from the RT2 PCR demonstrated a similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12 /MCP-5, CCL2 / MCP-1 were significantly attenuated by TQ (10μM). Also, in this study, consistent data were obtained for both protein antibody array densitometry and ELISA assays. In addition, TQ was found to reduce LPS mediated elevation in gene expression of Cxcl10 and a number of other cytokines in the panel. These findings demonstrate the significant anti-inflammatory properties of TQ in LPS activated microglial cells. Therefore, the obtained results might indicate the usefulness of TQ in delaying the onset of inflammation-mediated neurodegenerative disorders involving activated microglia cells.

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Neuronal injury induces microglial production of macrophage inflammatory protein‐1α in rat corticostriatal slice cultures

Cited by 13 publications

References 26 publications

Experimental autoimmune prostatitis induces microglial activation in the spinal cord

Experimental autoimmune prostatitis induces microglial activation in the spinal cord

Nrf2 deficiency leads to behavioral, neurochemical and transcriptional changes in mice

Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

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