Background
Interleukin-17A (IL17A) is a proinflammatory cytokine critically involved in autoimmune diseases, and monoclonal antibodies of IL17A have been approved for clinical treatment of psoriasis. However, a usable psoriatic animal model has been always required for preclinical evaluation of IL17A antagonists. Imiquimod (IMQ)-induced psoriasis model is widely used in fundamental research, but it’s not able to accurately show anti-psoriatic effect of IL17A antagonists with conventional modelling condition.
Results
On female C57BL/6 mice, with optimization on the usage of IMQ, positive control reagent and anti-mIL17A antibody, a 7-day model with proper testing window, acceptable disease severity as well as high repeatability was developed, and the efficacy of IL17A antagonist can be objectively evaluated by several qualitative and quantitative indices. Meanwhile, we validated the detailed involvement of IL17A signaling in disease progression, confirmed that the expression levels of IL17A and its related cytokines were induced by IMQ application, and its downstream cytokines can be inhibited by IL17A antagonist treatment. In further study, we revealed that IL17A was transient induced by IMQ and directly caused downstream signaling activation. This finding on the kinetical change of IL17A signaling will manifest the pharmacokinetics-pharmacodynamics investigation of IL17A antagonists.
Conclusions
Our work presents the application of a convenient psoriatic animal model in the research and development of IL17A antagonists, meanwhile providing extra evidence for understanding IL17A’s role in the progression of IMQ-induced psoriasis model, which manifest the research and development of IL17A antagonists.
Reaction of ozone with three kinds of olefins in air was studied. H2O2, CH3OOH, and HOCH2OOH were collected and analyzed with HPLC with a fluorometric detector. Direct reaction of CH2OO with H2O was found to be the source of HOCH2OOH. CH3OOH was formed only from the olefins which have a methyl group. Detailed reaction mechanisms are discussed.
Capillary electrophoresis (CE) methods for the determination of low-molecular-mass (LMM) carboxylic acids in airborne particular matter have been developed. The separations of 22 LMM carboxylic acids, including acids derived from the oxidation of biogenic hydrocarbons, are performed using a background electrolyte consisting of 3.0mM 2,6-naphthalenedicarboxylic acid and 18.0mM 2,2-bis (hydroxymethyl)-2,2',2"-nitrilotriethanol (Bis-tris) in 16% (v/v) 1-propanol within 10 min. Using a combination of a buffer mixed with an organic solvent and electroosmotic flow modifier, a minimum of peak overlaps is achieved with migration time variation of less than 1% and peak area ratio (relative to an internal standard) variation of less than 5% within 1 day. The detection limits for the aliphatic LMM acids that can be determined by this method are in the range of 30-140 micro g/L. Furthermore, a simple method for efficient extraction of LMM organic acids from particulate atmospheric matter collected on quartz fiber filters using high-volume samplers is developed. Combining the extraction procedure with a reduction of the extract to approximately 0.2 mL allows for the measurement of LLM in atmospheric particulate organic matter at concentrations well below 1 ng.m(-3). Repeat analysis of filters collected in tunnels, urban, suburban, and forested areas demonstrate that the procedure allows for measurements of aliphatic and aromatic LMM acids within a variability of 10-25%.
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