Xenobiotic transcription factors CncC and maf regulate expression of CYP321A16 and CYP332A1 that mediate chlorpyrifos resistance in Spodoptera exigua.

Insect cytochrome P450 s (P450 s) are associated with the metabolic detoxification of toxic xenobiotics and their constitutive upregulation is often associated with resistance to natural and synthetic toxicants. The P450 s CYP321A16 and CYP332A1 are constitutively overexpressed in an insecticide-resistant strain of beet armyworm, Spodoptera exigua. However, the function and upstream regulation of these two P450 s remain unknown. Here, we investigated the function of CYP321A16 and CYP332A1 in resistance to the organophosphate insecticide, chlorpyrifos and their regulation by the transcription factors CncC and Maf. Transgenic strains of Drosophila melanogaster expressing CYP321A16 or CYP332A1 showed higher levels of tolerance to chlorpyrifos than the control flies with the same genetic background. Furthermore, recombinant CYP321A16 and CYP332A1 proteins metabolized chlorpyrifos. Analysis of the putative promoter sequences of the genes coding for CYP321A16 and CYP332A1 revealed conserved CncC/Maf binding sites. Transfection of luciferase reporter plasmids containing the promoter of CYP450 gene together with CncC and Maf expression plasmids significantly enhanced the activity of the reporter. Promoter truncation identified a site in the promoter of CYP321A16 that is critical for the CncC/Maf binding. These data demonstrate that resistance to chlorpyrifos in S. exigua is conferred by the combined action of CYP321A16 and CYP332A1 and uncovered their regulation by the transcription factors CncC and Maf.

Metabolic syndrome affects narrow-band UVB phototherapy response in patients with psoriasis.

Psoriasis is a chronic inflammatory skin disease. Metabolic syndrome (MS) is a combination of central obesity, dyslipidemia, glucose intolerance, and elevated blood pressure. Many epidemiological surveys have revealed the association of psoriasis with MS. Narrowband ultraviolet radiation b (NB-UVB) is an effective and widely used treatment for psoriasis. The purpose of this study was to investigate whether the presence of MS in patient with psoriasis affects NB-UVB treatment and whether this syndrome correlates with systemic inflammation.From June 2016 to December 2016, 243 adults with a diagnosis of psoriasis vulgaris eligible to treatment with NB-UVB were admitted to the phototherapy unit of Dermatology department, Chinese PLA General Hospital. Fifty-five included patients were grouped based on the presence of MS. They accepted the treatment of NB-UVB and the following data were collected: serum levels of IL-17 (interleukin), TNF-α (tumor necrosis factor) and IL-6, Psoriasis Area and Severity Index (PASI) scores before and after 10 sections of NB-UVB treatment.Significant PASI improvement was observed in psoriatic patients without MS after 10 sections of phototherapy, while patients with MS showed a less improvement (P < .001). There was statistically significant difference in percentage of patients achieving 50% reduction in PASI scores between the 2 groups (P < .05). Multivariate logistic regression analysis showed MS was an independent factor that affecting the treatment of NB-UVB (P < .05). Psoriatic patients with MS showed a much less reduction of IL-17 and IL-6 before and after 10 sections of NB-UVB treatment respectively than patients without MS (P < .05).Psoriatic patients with MS have poorer improvement in comparison those without MS using NB-UVB treatment. MS was an independent factor that affecting the treatment of NB-UVB. In addition, psoriatic patients with MS showed a much less reduction of systemic biomarkers (interleukin-IL-17, TNF-α, IL-6) than patients without MS. Namely, they may need a longer course of treatment to achieve improved skin lesions.