Role of CD14‐positive cells in inflammatory cytokine and pain‐related molecule expression in human degenerated intervertebral discs

2020 ◽  
Author(s):  
Masayuki Miyagi ◽  
Kentaro Uchida ◽  
Shotaro Takano ◽  
Mitsufumi Nakawaki ◽  
Hiroyuki Sekiguchi ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Intervertebral Discs ◽  
Related Molecule ◽  
Degenerated Intervertebral Discs

scholarly journals Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes

2021 ◽  
Vol 22 (5) ◽  
pp. 2347
Author(s):  
Manu N. Capoor ◽  
Anna Konieczna ◽  
Andrew McDowell ◽  
Filip Ruzicka ◽  
Martin Smrcka ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Acne Vulgaris ◽  
Opportunistic Pathogen ◽  
Intervertebral Discs ◽  
Disc Disease ◽  
Gene Target ◽  
Cutibacterium Acnes ◽  
Pre Treatment

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

scholarly journals Elucidating the Complex Interactions between Stress and Epileptogenic Pathways

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Aaron R. Friedman ◽  
Luisa P. Cacheaux ◽  
Sebastian Ivens ◽  
Daniela Kaufer
Keyword(s):  
Experimental Data ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokine ◽  
Stress Hormones ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Complex Interactions ◽  
Narrow Focus ◽  
Analytical Tools

Clinical and experimental data suggest that stress contributes to the pathology of epilepsy. We review mechanisms by which stress, primarily via stress hormones, may exacerbate epilepsy, focusing on the intersection between stress-induced pathways and the progression of pathological events that occur before, during, and after the onset of epileptogenesis. In addition to this temporal nuance, we discuss other complexities in stress-epilepsy interactions, including the role of blood-brain barrier dysfunction, neuron-glia interactions, and inflammatory/cytokine pathways that may be protective or damaging depending on context. We advocate the use of global analytical tools, such as microarray, in support of a shift away from a narrow focus on seizures and towards profiling the complex, early process of epileptogenesis, in which multiple pathways may interact to dictate the ultimate onset of chronic, recurring seizures.

scholarly journals The pathophysiologic role of the protein kinase Cδ pathway in the intervertebral discs of rabbits and mice: In vitro, ex vivo, and in vivo studies

2012 ◽  
Vol 64 (6) ◽  
pp. 1950-1959 ◽  
Author(s):  
Michael B. Ellman ◽  
Jae-Sung Kim ◽  
Howard S. An ◽  
Jeffrey S. Kroin ◽  
Xin Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ex Vivo ◽  
Intervertebral Discs ◽  
In Vivo Studies ◽  
Protein Kinase Cδ

scholarly journals The Role of TTP Phosphorylation in the Regulation of Inflammatory Cytokine Production by MK2/3

2019 ◽  
Vol 203 (8) ◽  
pp. 2291-2300 ◽  
Author(s):  
Natalia Ronkina ◽  
Nelli Shushakova ◽  
Christopher Tiedje ◽  
Tatiana Yakovleva ◽  
Maxim A. X. Tollenaere ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Cytokine Production

scholarly journals GPR110 (ADGRF1) mediates anti-inflammatory effects of N-docosahexaenoylethanolamine

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Taeyeop Park ◽  
Huazhen Chen ◽  
Hee-Yong Kim
Keyword(s):  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Cytokine Expression ◽  
Regulatory Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Condition ◽  
Wild Type ◽  
Knock Out ◽  
The Brain

Abstract Background Neuroinflammation is a widely accepted underlying condition for various pathological processes in the brain. In a recent study, synaptamide, an endogenous metabolite derived from docosahexaenoic acid (DHA, 22:6n-3), was identified as a specific ligand to orphan adhesion G-protein-coupled receptor 110 (GPR110, ADGRF1). Synaptamide has been shown to suppress lipopolysaccharide (LPS)-induced neuroinflammation in mice, but involvement of GPR110 in this process has not been established. In this study, we investigated the possible immune regulatory role of GPR110 in mediating the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. Methods For in vitro studies, we assessed the role of GPR110 in synaptamide effects on LPS-induced inflammatory responses in adult primary mouse microglia, immortalized murine microglial cells (BV2), primary neutrophil, and peritoneal macrophage by using quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) as well as neutrophil migration and ROS production assays. To evaluate in vivo effects, wild-type (WT) and GPR110 knock-out (KO) mice were injected with LPS intraperitoneally (i.p.) or TNF intravenously (i.v.) followed by synaptamide (i.p.), and expression of proinflammatory mediators was measured by qPCR, ELISA, and western blot analysis. Activated microglia in the brain and NF-kB activation in cells were examined microscopically after immunostaining for Iba-1 and RelA, respectively. Results Intraperitoneal (i.p.) administration of LPS increased TNF and IL-1β in the blood and induced pro-inflammatory cytokine expression in the brain. Subsequent i.p. injection of the GPR110 ligand synaptamide significantly reduced LPS-induced inflammatory responses in wild-type (WT) but not in GPR110 knock-out (KO) mice. In cultured microglia, synaptamide increased cAMP and inhibited LPS-induced proinflammatory cytokine expression by inhibiting the translocation of NF-κB subunit RelA into the nucleus. These effects were abolished by blocking synaptamide binding to GPR110 using an N-terminal targeting antibody. GPR110 expression was found to be high in neutrophils and macrophages where synaptamide also caused a GPR110-dependent increase in cAMP and inhibition of LPS-induced pro-inflammatory mediator expression. Intravenous injection of TNF, a pro-inflammatory cytokine that increases in the circulation after LPS treatment, elicited inflammatory responses in the brain which were dampened by the subsequent injection (i.p.) of synaptamide in a GPR110-dependent manner. Conclusion Our study demonstrates the immune-regulatory function of GPR110 in both brain and periphery, collectively contributing to the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. We suggest GPR110 activation as a novel therapeutic strategy to ameliorate inflammation in the brain as well as periphery.

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