Doxycycline Attenuates Peripheral Inflammation in Rat Experimental Autoimmune Neuritis

Yi, Chenju; Zhang, Zhiyuan; Wang, Wei; Zug, Caroline; Schluesener, Hermann J.; Zhang, Zhiren

doi:10.1007/s11064-011-0522-2

Cited by 20 publications

(16 citation statements)

References 37 publications

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“…Doxycycline reduced inflammatory markers in as little as one week when administered to animals that already displayed robust inflammation, suggesting the treatment was not just preventing further inflammation, but resolving extant inflammation. The possibility does remain, however, that doxycyline is reducing inflammation directly, since doxycycline has been reported to have anti-inflammatory properties in its own right [59]–[62]. However, the observation that doxycycline appears to preferentially reduce human tau levels in a particular cortical layer and this is the same layer that shows the greatest reduction in GFAP staining suggests that at least some of the reduced inflammation observed with doxycycline treatment was a result of tau reduction.…”

Section: Discussionmentioning

confidence: 99%

Tau Overexpression Impacts a Neuroinflammation Gene Expression Network Perturbed in Alzheimer’s Disease

et al. 2014

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Filamentous inclusions of the microtubule-associated protein, tau, define a variety of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD). To better understand the role of tau-mediated effects on pathophysiology and global central nervous system function, we extensively characterized gene expression, pathology and behavior of the rTg4510 mouse model, which overexpresses a mutant form of human tau that causes Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We found that the most predominantly altered gene expression pathways in rTg4510 mice were in inflammatory processes. These results closely matched the causal immune function and microglial gene-regulatory network recently identified in AD. We identified additional gene expression changes by laser microdissecting specific regions of the hippocampus, which highlighted alterations in neuronal network activity. Expression of inflammatory genes and markers of neuronal activity changed as a function of age in rTg4510 mice and coincided with behavioral deficits. Inflammatory changes were tau-dependent, as they were reversed by suppression of the tau transgene. Our results suggest that the alterations in microglial phenotypes that appear to contribute to the pathogenesis of Alzheimer’s disease may be driven by tau dysfunction, in addition to the direct effects of beta-amyloid.

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Section: Discussionmentioning

confidence: 99%

Tau Overexpression Impacts a Neuroinflammation Gene Expression Network Perturbed in Alzheimer’s Disease

et al. 2014

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“…Tetracyclines, alone or in combination, have been used for the systemic treatment of HS . In various animal models, tetracyclines decreased Th17 differentiation and reduced IL‐17 levels …”

Section: Therapeutic Agents Affect the T Helper 17 Cell/regulatory T‐mentioning

confidence: 99%

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

et al. 2018

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“…Tetracyclines have been shown to have immunomodulatory and anti-inflammatory effects in several inflammatory conditions, such as multiples sclerosis, Parkinson’s disease and rheumatoid arthritis57585960. Furthermore, doxycycline suppressed the proliferation of lymphocytes61 and minocycline inhibited proliferation and reduced production of IL-2, IFNγ and TNFα in human T-cells62.…”

Section: Discussionmentioning

confidence: 99%

Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

Becker

Bengs

Aluri³

et al. 2016

Sci Rep

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1Inflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we studied in mice whether doxycycline, metronidazole or isotretinoin induce epigenetic modifications, and consequently change T-cell mRNA expression and/or function directly after treatment and after a 4 week recovery period. Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. Metronidazole activated processes associated with anti-inflammatory pathways in both T-cell subsets directly after the treatment period whereas doxycycline induced an immediate proinflammatory expression profile that resolved after the recovery period. Long-term changes indicated an inhibition of proliferation by doxycycline and induction of beneficial immune and metabolic pathways by metronidazole. Persistent alterations in microRNA and mRNA expression profiles after the recovery period indicate that all three medications may induce long-term epigenetic modifications in both T-cell subsets. Yet, our data do not support the induction of a long-term pro-inflammatory phenotype in murine Tregs and naive T-cells.Inflammatory bowel diseases (IBD) with the two main forms, Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammatory conditions of the gastrointestinal tract that affect an increasing number of patients worldwide 1 . The precise pathogenesis of IBD is multifactorial and is not completely elucidated yet. It is generally considered that environmental factors represent an important contributor to the pathogenesis of IBD by triggering an inappropriate and progressive immune response to the commensal gut microbiota in a genetically predisposed host 2 . To date, genome-wide association studies have identified more than 240 IBD susceptibility loci, affecting genes involved in immune regulation, mucosal immune response, autophagy and epithelial barrier function [3][4][5] . Currently available data support the concept that IBD is a polygenic disease and suggest that non-genetic modifications involved in regulatory processes might have an impact on susceptibility and severity of disease 6 . Mechanisms of gene regulation that do not alter the basic sequence of DNA are called epigenetic regulations and have been studied extensively over the last few years. These studies have shown that epigenetic modifications are associated with a variety of diseases, e.g. IBD 7,8 , multiple sclerosis 9 , psoriasis 10 and systemic lupus erythematosus 11. The molecular basis of epigenetic regulation is complex. Importantly, changes may remain through cell division, and last for many generations (long-term effects) 12 . So far, th...

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Doxycycline Attenuates Peripheral Inflammation in Rat Experimental Autoimmune Neuritis

Cited by 20 publications

References 37 publications

Tau Overexpression Impacts a Neuroinflammation Gene Expression Network Perturbed in Alzheimer’s Disease

Tau Overexpression Impacts a Neuroinflammation Gene Expression Network Perturbed in Alzheimer’s Disease

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

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