International journal of molecular medicine
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The aim of the present study was to investigate the role of complement activation in the pathogenesis of neuropathic pain (NPP) induced by peripheral nerve injury. We modified a classical chronic constriction injury (CCI) model (mCCI), and verified its reliability in rats. Furthermore, reverse transcription-PCR and immunohistochemistry were conducted to investigate complement activation in the spinal dorsal horn and the effect of a complement inhibitor, cobra venom factor (CVF), on the behavior of the mCCI model rats. ⋯ Transmission electron micrographs revealed mitochondrial swelling, cell membrane damage, and cristae fragmentation in the neurons of the spinal dorsal horn 14 days after mCCI. Mitochondrial swelling was attenuated in mCCI rats receiving CVF. The findings demonstrated that abnormal complement activation occurred in the dorsal horn of the spinal cord in rats with NPP, and C3 in the spinal dorsal horn could play an important role in the cascade reaction of complements that are involved in the development of hyperalgesia.
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The pharmacologically-induced expression of the γ-globin gene, to increase fetal hemoglobin (HbF) production, is a therapeutic strategy used for the treatment of β-thalassemia and sickle cell anemia (SCA). The aim of this study was to investigate the effects of Plastrum testudinis (PT) on differentiation, proliferation, γ-globin gene expression and HbF synthesis in human erythroid cells. For this purpose, we used the K562 human leukemia cell line and human erythroid progenitor cells from normal donors and patients with β-thalassemia cultured using the two-phase liquid culture system. ⋯ These effects were suppressed by pre-treatment with the p38 MAPK inhibitor, SB203580. Epigenetic histone modifications within γ-globin gene promoter regions, via activation of the p38 MAPK signaling pathway, are important for the induction of γ-globin gene expression in human erythroid cells by PT. PT may be a novel potential therapeutic agent for β-hemoglobinopathies, including β-thalassemia and SCA.
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Mesenchymal stem cells (MSCs) have been successfully used for the treatment of experimental intracerebral hemorrhage (ICH). However, the neuroprotective mechanisms through which MSCs improve neurological functional recovery are not fully understood. In the present study, we tested the hypothesis that treatment with MSCs inhibits inflammation after ICH and reduces subsequent brain injury. ⋯ Consistently, we found a significant anti-inflammatory effect of Flk-1(+) hBMSCs on the ICH brain, including a decrease in neutrophil infiltration and microglial activation in the peri-ICH area, and downregulation of inflammatory mediators, such as interleukin (IL)-1β, IL-2, IL-4, IL-6, and tumor necrosis factor (TNF)-α. In addition, Flk-1+ hBMSC treatment significantly increased vascular density in the peri-ICH area, and transplanted Flk-1(+) hBMSCs were found to be incorporated into the cerebral vasculature 55 days after transplantation. Overall, these data suggest an essential role for Flk-1(+) hBMSCs in reducing inflammatory infiltration, promoting angiogenesis, and improving functional recovery after ICH in rats.
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Metallothioneins (MTs) are a family of cysteine-rich low molecular-weight proteins that can act as reactive oxygen species scavengers. Although it is known that the induction of MT expression suppresses various inflammatory disorders, the role of MTs in intestinal inflammation remains unclear. In this study, we investigated the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the MT-I/II genes. ⋯ MT-positive cells were detected in the lamina propria and submucosal layer by immunohistochemical and immunofluorescence staining, and were mainly co-localized in F4/80-positive macrophages. The production of inflammatory cytokines (TNF-α, IFN-γ and IL-17) from isolated peritoneal macrophages increased following lipopolysaccharide stimulation, and these increases were significantly enhanced in the macrophages obtained from the MT-I/II knockout mice. These data indicate that MTs play an important role in the prevention of colonic mucosal inflammation in a mouse model of DSS-induced colitis, thus suggesting that endogenous MTs play a protective role against intestinal inflammation.
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microRNAs (miRNAs) play a crucial role in tissue development and the pathology of various diseases. However, the effects and roles of miRNAs in macrophage polarization have yet to be investigated. ⋯ The differential expression of selected miRNAs was validated by real-time qRT-PCR: miR-181a, miR-155-5p, miR-204-5p and miR-451 were upregulated (fold change >2, P<0.05) and miR-125-5p, miR-146a-3p, miR-143-3p and miR-145-5p were downregulated (fold change <-2, P<0.05) in M1 compared with M2. In conclusion, our study may be useful for exploring the precise roles of miRNAs in macrophage differentiation and polarized activation processes in the future.