Aminooxy acetic acid suppresses Th17-mediated psoriasis-like skin inflammation by inhibiting serine metabolism

Abstract

Background: Psoriasis is a common chronic inflammatory skin disease characterized by an external red rash that is caused by abnormal proliferation and differentiation of keratinocytes and immune T cells. This study aimed to elucidate the role of aminooxy acetic acid (AOA) in alleviating psoriasis from the perspective of immunology and metabolomics. Therefore, contributing to the development of new drugs as candidates for psoriasis treatment.Methods: To investigate the symptom-alleviating effects and the related mechanisms of AOA on the treatment of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin mouse model and interleukin (IL)-17-stimulated human keratinocytes.Results: The results showed that AOA ameliorated psoriasis-related symptoms and decreased inflammation-associated antimicrobial peptides and T-helper 17 (Th17)-associated cytokines in a mouse model of psoriasis. Furthermore, AOA inhibited the activation of mechanistic target of rapamycin (mTOR) by suppressing serine metabolism-related genes. Importantly, mTOR inhibition ameliorated psoriatic disease by affecting the differentiation of various T cells and normalizing the Th17/regulatory T (Treg) cell balance. In addition, IL-17-stimulated human keratinocytes showed the same results as in the in vivo experiments.Conclusion: Taken together, these results suggest that targeting the serine metabolism pathway in the treatment of psoriasis is a novel strategy, and that AOA could be utilized as a novel biologic to treat psoriasis.

Imidazole propionate ameliorates atopic dermatitis-like skin lesions by inhibiting mitochondrial ROS and mTORC2

“…Total RNA was extracted from cultured cells and frozen tissues using the RNAIso Plus Reagent (Takara, Tokyo, Japan) according to the manufacturer’s instructions. cDNA synthesis and RT-qPCR analyses were performed as described previously ( 42 ). The RNA samples were dissolved in RNase-free water (Thermo Fisher Scientific) and purified by phenol/chloroform extraction.…”

“…Cell lysates were prepared and western blotting was performed as described previously ( 42 ). Proteins were separated using 6%, 10%, or 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis.…”

The new era of immune skin diseases: Exploring advances in basic research and clinical translations

“…Metabolomics also provides new ideas for the treatment of psoriasis. In mice, aminooxy acetic acid (AOA) could alleviate psoriasis symptoms by impacting the Th17-associated passway, suggesting a new therapeutic target [ 106 ]. Chen et al found that a higher level of L-carnitine (LC(C0)) can reduce skin thickness and Th17 infiltration in IMQ-induced mice, suggesting that supplementing with LC(C0) could be a viable therapeutic approach for treating psoriasis [ 107 ].…”

Network pharmacology and gut microbiota insights: unraveling Shenling Baizhu powder’s role in psoriasis treatment

“…The pathogenesis of psoriasis is complex and multifactorial, involving genetic predisposition, immunological dysregulation, and environmental triggers. Recent advances in understanding the pathophysiology of psoriasis have highlighted the role of T-helper cells, particularly Th17 cells ( Guo et al, 2023 ; Lee et al, 2023 ), in driving the inflammatory cascade that characterizes this disease.…”