ABSTRACT
Antigen-primed T cells respond to restimulation much faster than naïve T cells and form the cellular basis of immunological memory. The formation of memory Th2 cells starts when naïve CD4 T cells are transformed into effector Th2 cells and is completed after antigen clearance and a long-term resting phase accompanied by epigenetic changes in the Th2 signature genes. Memory Th2 cells maintain their functions and acquired heterogeneity through epigenetic machinery, on which the recall-response of memory Th2 cells is also dependent. We provide an overview of the epigenetics in the whole Th2 cell cycle, mainly focusing on two different histone lysine methyltransferase complexes: the Polycomb and Trithorax groups. We finally discuss the pathophysiology and potential therapeutic strategies for the treatment of Th2-mediated inflammatory diseases in mice and humans.
Subject(s)
Epigenesis, Genetic/immunology , Gene Expression Regulation/immunology , Immunologic Memory/immunology , Th2 Cells/immunology , Animals , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cell Differentiation/genetics , Cell Differentiation/immunology , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/immunology , Histone-Lysine N-Methyltransferase/metabolism , Humans , Immunologic Memory/genetics , Inflammation/genetics , Inflammation/immunology , Inflammation/therapy , Th2 Cells/metabolismABSTRACT
The use of natural products in wound healing has been extensively studied in the context of complementary and alternative medicine. Propolis, a natural product, is a polyphenol-rich resin used for this purpose. This study aimed to investigate the effect of Brazilian Red Propolis Extract (BRPE) on inflammation and wound healing in mice, using a tissue repair model. The BRPE polyphenol content was analyzed by liquid chromatography coupled to mass spectrometry (LC/MS). A full-thickness excision lesion was created, and mice were treated orally with daily doses of vehicle solution (water-alcohol solution containing 2% of ethanol, control group) or 100mg/kg of BRPE (P100 group) during nine consecutive days. BRPE chemical composition analysis showed that this complex matrix contains several phenolic compounds such as phenolic acids, phenolic terpenes and flavonoids (especially catechins, flavonols, chalcones, isoflavones, isoflavans, pterocarpans and bioflavonoids). After BRPE administration, it was observed that, when compared to the control group, P100 group presented faster wound closure (p<0.001); less neutrophils per mm2 (p<0.05) and macrophages (p<0.01) in tissue analyses, down regulation of the inflammatory transcription factor pNF-κB protein expression, and reduced production of inflammatory cytokine, such as TGF-ß, TNF-α (p<0.0001), and IL-6 (p<0.001). These findings suggest a positive role of BRPE oral administration in the wound healing process via suppressing the inflammatory response during tissue repair.
Subject(s)
Inflammation Mediators/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Plant Extracts/pharmacology , Propolis , Skin/drug effects , Wound Healing/drug effects , Animals , Brazil , Inflammation Mediators/metabolism , Male , Mice , NF-kappa B/metabolism , Plant Extracts/isolation & purification , Skin/injuries , Skin/metabolism , Wound Healing/physiologyABSTRACT
Acetaminophen(APAP)is the most wideIy-used anaIgesic drug cIinicaIIy. It is aIso the most risky agent for hepatotoxicity. It has been wideIy used as a modeI drug to study mechanisms of chemicaI-induced Iiver injury and to test the hepatoprotective potentiaI of chemicaIs. This review summa-rized the intraceIIuIar events of acetaminophen-induced hepatotoxicity,incIuding metaboIic activation, ceIIuIar damage,c-Hun N-terminaI kinase pathway,and modified metaboIism function,and additionaIIy focused on the roIe of infIammatory factors and ceIIs in APAP hepatotoxicity,as weII as protection strate-gies of chemicaIs and naturaI products.
