ABSTRACT
BACKGROUND: Inflammatory chemokines, such as macrophage-derived chemokine (MDC/CCL22), are elevated in the serum and lesioned skin of patients with atopic dermatitis (AD), and are ligands for C-C chemokine receptor 4, which is predominantly expressed on T helper 2 lymphocytes, basophils and natural killer cells. We have previously reported that quercetagetin has an inhibitory activity on inflammatory chemokines, which is induced by interferon (IFN)-γ and tumour necrosis factor (TNF)-α, occurring via inhibition of the signal transducer and activator of transcription 1 (STAT1) signal. OBJECTIVES: To investigate the specific mechanisms of quercetagetin on the STAT1 signal. METHODS: We confirmed the inhibitory activity of quercetagetin on MDC and STAT1 in HaCaT keratinocytes. The interaction between STAT1 and IFN-γR1 was investigated using immunoprecipitation. The small interfering RNA approach was used to investigate the role of suppressor of cytokine signalling 1 (SOCS1) and transforming growth factor (TGF)-ß1 induced by quercetagetin. RESULTS: Quercetagetin inhibited the expression of MDC at both the protein and mRNA levels in IFN-γ- and TNF-α-stimulated HaCaT human keratinocytes. Moreover, quercetagetin inhibited the phosphorylation of STAT1 through upregulation of SOCS1. Increased expression of SOCS1 disrupted the binding of STAT1 to IFN-γR1. Furthermore, quercetagetin augmented the expression of TGF-ß1, which is known to modulate the immune response and inflammation. CONCLUSIONS: These results suggest that quercetagetin may be a potent inhibitor of the STAT1 signal, which could be a new molecular target for anti-inflammatory treatment, and may thus have therapeutic applications as an immune modulator in inflammatory diseases such as AD.
Subject(s)
Chemokine CCL22/antagonists & inhibitors , Chromones/pharmacology , Keratinocytes/drug effects , STAT1 Transcription Factor/drug effects , Transforming Growth Factor beta1/drug effects , Flavones , Humans , Interferon-gamma/drug effects , Janus Kinases/drug effects , Receptors, Interferon/drug effects , Signal Transduction/drug effects , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins/drug effects , Tumor Necrosis Factor-alpha/drug effects , Interferon gamma ReceptorABSTRACT
We formed a DNA network embedding ferromagnetic cobalt nanoparticles with a 12-nm diameter through a nanoscale self-assembly of DNA molecules on large-scale mica surfaces (12 mm x 12 mm); we then confirmed its structural characteristics with an atomic force microscope. Moreover, noncontact magnetic force microscope measurement revealed that some embedded cobalt nanoparticles have different directions of magnetization, similar to "bits" in magnetic data storage devices.
