IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A–transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A–transgenic mice were treated with plasmid coding human IL-37 sequence–formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.
Prenylflavonoids are valuable natural products that are widely distributed in plants. They often possess divergent biological properties, including phytoestrogenic, anti‐bacterial, anti‐tumor, and anti‐diabetic activities. The reaction catalyzed by prenyltransferases represents a Friedel–Crafts alkylation of the flavonoid skeleton in the biosynthesis of natural prenylflavonoids and often contributes to the structural diversity and biological activity of these compounds. However, only a few plant flavonoid prenyltransferases have been identified thus far, and these prenyltransferases exhibit strict substrate specificity and low catalytic efficiency. In this article, a flavonoid prenyltransferase from Sophora flavescens, SfFPT, has been identified that displays high catalytic efficiency with high regiospecificity acting on C‐8 of structurally different types of flavonoid (i.e., flavanone, flavone, flavanonol, and dihydrochalcone, etc.). Furthermore, SfPFT exhibits strict stereospecificity for levorotatory flavanones to produce (2S)‐prenylflavanones. This study is the first to demonstrate the substrate promiscuity and stereospecificity of a plant flavonoid prenyltransferase in vitro. Given its substrate promiscuity and high catalytic efficiency, SfFPT can be used as an environmentally friendly and efficient biological catalyst for the regio‐ and stereospecific prenylation of flavonoids to produce bioactive compounds for potential therapeutic applications.
The uptake by plants from soil is one of the first steps for hexachlorocyclohexane (HCH) isomers to enter the food web. However, the HCH transformation associated with the uptake process is still not well understood. Therefore, a soil−wheat pot experiment was conducted to characterize the HCH transformation during wheat growth using compound-specific isotope analysis (CSIA) and enantiomer fractionation. The results showed that the δ 13 C and δ 37 Cl values of β-HCH remained stable in soil and wheat, revealing no transformation. In contrast, an increase of δ 13 C and δ 37 Cl values of α-HCH indicated its transformation in soil and wheat. A shift of the enantiomer fraction (EF) (−) from 0.50 to 0.35 in soil at the jointing stage and 0.35 to 0.57 at the harvest stage suggested that the preferential transformation of enantiomers varied at different growth stages. Based on the dual element isotope analysis, the transformation mechanism in the soil−wheat system was different from that in wheat in hydroponic systems. The high abundance of HCH degraders, Sphingomonas sp. and Novosphingobium sp., was detected in the α-HCH-treated rhizosphere soil, supporting the potential for biotransformation. The application of CSIA and EF allows characterizing the transformation of organic pollutants such as HCHs in the complex soil−plant systems.
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