Mustard Seed Attenuates Imiquimod-induced Psoriasiform Inflammation Of BALB/c Mice

Background and objectives:Recently, it’s been found that innate immune system plays pivotal roles in psoriasis,of which the role of plasmacytoid dendritic cells (pDC) attracts more and moreintrests of scientists. pDC is the main source of type I interferon (IFN-α/β).Imiquimod (IMQ) is a specific activator of TLR7/8. Topical application of IMQinduces a psoriasiform inflammation of BALB/c mice, which depending on the IFN-α,IL-23/IL-17axis and IL-22. This is a promising mouse model of psoriasis which isinduced in a natural immune state compared to the xenograft, trangenic or geneknockout mouse model. The present therapies of psoriasis are symptomatic, and needa long duration of treatment with poor compliance of patients. So it is urgent toexplore more acceptable therapies of psoriasis. Mustard seed (MS) belongs to theCruciferae Brassica. MS has been validated to possess anticancer andanti-inflammatory effects.Our recent study has revealed that MS possesses thebioactivity of antagonizing allergic contact dermatitis (ACD). The effects of MS onpsoriasis is not certain until now. Thus, it is very meaningful to elucidate the effects ofMS on IMQ-induced psoriasiform inflammation (IPI) and the mechanisms of action.Methods:1. Animal experiments: establishment of IPI model; observation of the effects ofMS and i.p. injection of PDTC on the IPI;2.HE staining was used to observe the histopathological changes of lesions;3.Immunohistochemistry was used to investigate the lesional infiltrates of T cells,pDC and macrophage and expression of iNOS; Flowcytometry was used toinvestigate the changes of percentage of T cells, pDC and macrophage in isolatedcells from spleen.4.colorimetric analysis was used to detect the activities of plasma SOD, CAT,GSH-PX and MDA; 5.RT-PCR was used to detect the mRNA expression of IFN-α、IL-17A/F and IL-22in lesions; ELISA was used to detect the serum IFN-α、IL-17and IL-22.Results:1.MS attenuated obviously IPI, but did not clear it completely;2.MS reduced infiltrations of T cells, pDC and macrophages in lesions; reducedpercentages of pDC and macrophages and increased percentage of CD4+T cells andthe ratio of CD4+/CD8+T cells in the isolated immunocytes from spleen.3.The activities of SOD, CAT and GSH-PX were reduced and content of MDA andlesional expression of iNOS were increased in IPI mice compared to those in controlmice; MS reverses all above changes with the amelioration of IPI.4.MS reduced significantly the expressions of IFN-α, IL-17and IL-22at mRNAand protein levels compared to those of IPI, dynamic analysis of the expressions ofmRNAs indicated significant differences from day2-4onward of topical applicationof IMQ;5.MS reduced the content of lesional NF-κB p65; i.p. injection of PDTC alsoattenuated IPI, of which the plasma activities of SOD,CAT and GSH-PX and contentof MDA, lesional relative quantities of IFN-α,IL-17A/F, IL-22mRNA were notdifferent significantly from those of MS group mice, but lesional mRNAs were higherthan those of control mice, p<0.01.Conclusions:MS attenuates obviously the IPI of BALB/c mice, reducing the infiltrations of Tcells, pDC and macrophages, oxidative status and cytokines such as IFN-α, IL-17andIL-22. These results provide a basis for MS to be a promising intervention of psoriasisin the future.