Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut

Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T reg- ulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for mod- ulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43. Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry. Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. Conclusion: C43 can modulate the immune response through the intestine by promoting the im- munosuppressive Treg population

Chemical Profiling, Bioactivity Evaluation and the Discovery of a Novel Biopigment Produced by <i>Penicillium purpurogenum</i> CBS 113139

Biobased pigments are environmentally friendly alternatives to synthetic variants with an increased market demand. Production of pigments via fermentation is a promising process, yet optimization of the production yield and rate is crucial. Herein, we evaluated the potential of Penicillium purpurogenum to produce biobased pigments. Optimum sugar concentration was 30 g/L and optimum C:N ratio was 36:1 resulting in the production of 4.1–4.5 AU (namely Pigment Complex A). Supplementation with ammonium nitrate resulted in the production of 4.1–4.9 AU (namely Pigment Complex B). Pigments showed excellent pH stability. The major biopigments in Pigment Complex A were N-threonyl-rubropunctamin or the acid form of PP-R (red pigment), N-GABA-PP-V (violet pigment), PP-O (orange pigment) and monascorubrin. In Pigment Complex B, a novel biopigment annotated as N-GLA-PP-V was identified. Its basic structure contains a polyketide azaphilone with the same carboxyl-monascorubramine base structure as PP-V (violet pigment) and γ-carboxyglutamic acid (GLA). The pigments were not cytotoxic up to 250 μg/mL