Anti-L Kynurenine monoclonal antibody, clone MAPW6C8

Indoleamine 2,3-dioxygenase 1(IDO1) is an enzyme known to suppress immune responses, and several reports have showed that it is associated with psoriasis.IDO2is an isoform ofIDO1, recently identified as a catalytic enzyme in the tryptophan-kynurenine pathway, which is expressed in dendritic cells and monocytes. The expression ofIDO2in immune cells suggests thatIDO2may contribute to immune functions. However, the role ofIDO2in the pathogenesis of psoriasis remains unclear. In this study, to elucidate the role ofIDO2in psoriasis, we assessed imiquimod (IMQ)-induced psoriasis-like dermatitis inIDO2knockout (KO) mice. Skin inflammation, evaluated by scoring erythema, scaling, and ear thickness, was significantly worse in theIDO2KO mice than in the wild-type (WT) mice. The mRNA expression levels of TNF-alpha, IL-23p19, and IL-17A, key cytokines involved in the development of psoriasis, were also increased in theIDO2KO mice. Furthermore, immunohistochemistry revealed that the number of Ki67-positive cells in the epidermis and CD4-, CD8-, and IL-17-positive lymphocytes infiltrating the dermis were significantly increased in theIDO2KO mice. These results suggest thatIDO2might decrease IL-17 expression, thereby resulting in the suppression of skin inflammation in IMQ-induced psoriasis-like dermatitis.

Perinatal exposure to bisphenol A (BPA) contributes to neurological disorders in offspring, but the underlying mechanisms are still poorly understood. The abnormal release of neuroactive metabolites in the tryptophan (TRP) and dopamine (DA) pathways is considered to be closely associated with some disorders. Thus, in this study, TRP and DA pathways in adult female mouse offspring were investigated when the pregnant mice were given either vehicle or BPA (2, 10, or 100 mu g/kg/d) from day 6 of gestation until weaning. Then, the serum and brain samples of offspring were collected at 3, 6 and 9 months, and 12 neuroactive metabolites in the TRP and DA pathways were detected. The results showed that, in the TRP pathway, TRP levels decreased, whereas kynurenine (KYN) levels and TRP turnover increased in the brain. In the serum, TRP, KYN and 5-hydroxytryptamine (5-HT) levels decreased significantly. For the DA pathway, DA and DA metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA), reduced significantly in the brain and serum. DA turnover decreased dramatically in the brain but enhanced in the serum. The disturbance of these two metabolic pathways might be one of the potential mechanisms of BPA-induced neuropsychiatric disorders. (C) 2020 Elsevier Ltd. All rights reserved.