Allelopathic inhibition effects and mechanism of phenolic acids to Microcystis aeruginosa.

Allelochemicals are essential agents for the biological control of harmful blooms. It is crucial to identify efficient algal suppressors and understand their mechanisms. This study reports the inhibition of Microcystis aeruginosa growth by 6 phenolic acids derived from plants' secondary metabolites. The inhibitory effect of phenolic acids was significantly influenced by exposure dose and phenolic acid species. Caffeic acid has the most efficient algal inhibition ability (96 h-EC50 of 5.8 mg/L). In contrast, the other 5 analogs (cinnamic acid, p-coumaric acid, 3-hydroxycinnamic acid, ferulic acid, and isoferulic acid) showed a weak inhibition effect or promotion effect with the exposure dose of 5-100 mg/L. ROS and chlorophyll a content tests combined with metabolomics analysis revealed that caffeic acid could induce the ROS accumulation of M. aeruginosa. They mainly disturbed nucleotide, amino acid, and fatty acid metabolism, leading to the downregulation of most metabolites, including toxins of microcystin LR and cyanopeptolin A, and the precursors of some unpleasant terpenoids. It has been suggested that caffeic acid is an effective agent for controlling M. aeruginosa blooms.

STEAP4 expression in CNS resident cells promotes Th17 cell-induced autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is a debilitating neurological disease caused by autoimmune destruction of the myelin sheath. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for the pathogenesis of MS. We and others have previously demonstrated that IL-17 is critical for the pathogenesis of EAE. The concentration of IL-17 is significantly higher in the sera of MS patients than in healthy controls and correlates with disease activity. Moreover, anti-IL-17 neutralizing antibody demonstrated promising efficacy in a phase II trial in MS patients, further substantiating a key pathogenic role for IL-17 in MS. While Th17 and IL-17 are emerging as a bona fide drivers for neuroinflammation, it remains unclear what effector molecule executes the inflammatory tissue destruction in Th17-driven EAE. METHODS: By microarray analysis, we found STEAP4 is a downstream molecule of IL-17 signaling in EAE. We then used STEAP4 global knockout mice and STEAP4 conditional knockout mice to test its role in the pathogenesis of EAE. RESULTS: Here, we report that the metalloreductase, STEAP4, is a key effector molecule that participates and contributes to the pathogenesis of Th17-mediated neuroinflammation in experimental autoimmune encephalomyelitis. STEAP4 knockout mice displayed delayed onset and reduced severity of EAE induced by active immunization. The reduced disease phenotype was not due to any impact of STEAP4 deficiency on myelin reactive T cells. In contrast, STEAP4 knockout mice were resistant to passively induced EAE, pointing to a role for STEAP4 in the effector stage of EAE. Notably, STEAP4 was only induced the spinal cord of EAE mice that received Th17 cells but not Th1 cells. Consistently, STEAP4 deficiency protected from only Th17 but not Th1-induced EAE. Finally, using Nestin-Cre STEAP4fl/fl mice, we showed that ablation of STEAP4 expression in the resident cells in the central nervous system attenuated disease severity in both active immunization and passive Th17 transfer-induced EAE. CONCLUSION: In this study, we identified STEAP4 as a Th17-specific effector molecule that participates and contributes to the pathogenesis of neuroinflammation, thus potentially provide a novel target for MS therapy.