Brain, behavior, and immunity
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Brain Behav. Immun. · Feb 2015
Molecular mechanisms of repeated social defeat-induced glucocorticoid resistance: Role of microRNA.
Glucocorticoid (GC) resistance is a severe problem associated with various inflammatory diseases. Previous studies have shown that repeated social stress induces GC resistance in innate immune cells, but the underlying molecular mechanisms have not been fully elucidated. Therefore, the purpose of this study was to examine potential underlying molecular mechanism(s) of repeated social defeat (RSD) stress on GC resistance in splenic macrophages. ⋯ Among these miRNAs, we verified direct effects of miRNA-29b and -340 overexpression on mRNA expression of GC receptors in L929 cells. The overexpression of miRNA-29b or -340 in L929 cells significantly reduced LPS-induced overexpression of GC receptors. In conclusion, this study provides evidence that epigenetic regulation, such as DNA methylation and miRNA expression, may play a role in the RSD-induced GC resistance that we have observed in splenic macrophages.
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Brain Behav. Immun. · Feb 2015
Acute increases in intramuscular inflammatory cytokines are necessary for the development of mechanical hypersensitivity in a mouse model of musculoskeletal sensitization.
Musculoskeletal pain is a widespread health problem in the United States. Back pain, neck pain, and facial pain are three of the most prevalent types of chronic pain, and each is characterized as musculoskeletal in origin. Despite its prevalence, preclinical research investigating musculoskeletal pain is limited. ⋯ The role of individual cytokines in mechanical hypersensitivity following musculoskeletal sensitization was assessed using knockout mice lacking components of the IL-1, IL-6 or TNF systems. Collectively, our data demonstrate that acidified saline injection increases intramuscular IL-1 and IL-6, but not TNF; that intramuscular pre-treatment with an NF-κB inhibitor blocks mechanical hypersensitivity; and that genetic manipulation of the IL-1 and IL-6, but not TNF systems, prevents mechanical hypersensitivity following musculoskeletal sensitization. These data establish that actions of IL-1 and IL-6 in local muscle tissue play an acute regulatory role in the development of mechanical hypersensitivity following musculoskeletal sensitization.