ABSTRACT
Atopic dermatitis (AD) is a skin condition caused by an imbalance of distinct subsets of T helper cells. Previously, we showed that 4-hydroxy-3-methoxycinnamaldehyde (4H3MC) inhibits T cell activation but does not induce apoptosis. Here, we examined the mechanism underlying the inhibitory effect of 4H3MC on AD both in vivo and in vitro. We sought to test the pharmacological effects of 4H3MC using a mouse model of 2, 4-'2,4-dinitrocholorobenzene' (DNCB)- and mite-induced AD. Also, we determined whether 4H3MC affects T cell differentiation and proliferation. Oral administration of 4H3MC attenuated the symptoms of DNCB- and mite-induced AD, including increased ear thickness, serum IgE levels, immune cell infiltration into inflammatory lesions, and pathogenic cytokine expression in ear tissues. In vitro, 4H3MC blocked T cell differentiation into Th1 and Th2 subtypes, as reflected by suppression of T-bet and GATA3, which are key transcription factors involved in T cell differentiation. In addition, 4H3MC downregulated T cell proliferation during Th1 and Th2 differentiation and keratinocyte activation. Collectively, these findings suggest that 4H3MC ameliorates AD symptoms by modulating the functions of effector T cells and keratinocytes.
Subject(s)
Acrolein/analogs & derivatives , Dermatitis, Atopic/prevention & control , Keratinocytes/drug effects , T-Lymphocytes/drug effects , Acrolein/administration & dosage , Acrolein/pharmacology , Administration, Oral , Animals , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cytokines/genetics , Cytokines/metabolism , Dermatitis, Atopic/immunology , Dinitrochlorobenzene/immunology , Female , GATA3 Transcription Factor/genetics , GATA3 Transcription Factor/metabolism , Gene Expression/drug effects , Inflammation Mediators/metabolism , Keratinocytes/metabolism , Mice, Inbred BALB C , Mice, Inbred C57BL , Mites/immunology , Reverse Transcriptase Polymerase Chain Reaction , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism , T-Lymphocytes/metabolism , Th1 Cells/drug effects , Th1 Cells/metabolism , Th2 Cells/drug effects , Th2 Cells/metabolismABSTRACT
The present study aimed to examine the anti-inflammatory effects and potential mechanism of action of Artemisia asiatica Nakai (A. asiatica Nakai) extract in activated murine macrophages. A. asiatica Nakai extract showed dose-dependent suppression of lipopolysaccharide (LPS)-induced nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 activity. It also showed dose-dependent inhibition of nuclear factor-κB (NF-κB) translocation from the cytosol to the nucleus and as an inhibitor of NF-κB-alpha phosphorylation. The extract's inhibitory effects were found to be mediated through NF-κB inhibition and phosphorylation of extracellular signal-regulated kinase 1/2 and p38 in LPS-stimulated J774A.1 murine macrophages, suggesting a potential mechanism for the anti-inflammatory activity of A. asiatica Nakai. To our knowledge, this is the first report of the anti-inflammatory effects of A. asiatica Nakai on J774A.1 murine macrophages; these results may help develop functional foods possessing an anti-inflammatory activity.
