Biology subjects

Murata, R.

Publications and source records attributed to Murata, R..

2 recordsLinked to original sources

bioRxiv2023

Retrospective Evaluation of the Eye Irritation Potential of Agrochemical Formulations

While multiple in vitro eye irritation methods have been developed and adopted as OECD health effects test guidelines, only one is considered a complete replacement for the in vivo rabbit eye test for classification and labelling for eye irritation hazard. Additionally, for most of the adopted methods there is a data gap on the applicability to predict the ocular irritation potential of agrochemical formulations. To overcome this data gap, a retrospective evaluation of 192 agrochemical formulations with in vivo (OECD TG 405) or in vitro (OECD TG 437, 439, or 492) data was conducted to determine if the in vitro methods could accurately assign United Nations Globally Harmonized System for Classification and Labelling of Chemicals (GHS) eye irritation hazard classifications. In addition, for each of the final formulations and their individual components, we also conducted an evaluation of the GHS concentration threshold (CT) approach. The results herein suggest that the four individual methods and GHS CT approach were highly predictive of formulations that would not require classification for eye irritation hazard. Given most agrochemical formulations fall into this category, methods that accurately identify not classified mixtures could significantly reduce the use of animals for this endpoint.

pharmacology and toxicology↗

bioRxiv2022

G307S DNAM-1 mutation exacerbates autoimmune encephalomyelitis via enhancing CD4+ T cell activation

Although rs763361, which causes a non-synonymous glycine-to-serine mutation at residue 307 (G307S mutation) of the DNAM-1 immunoreceptor, is a single-nucleotide polymorphism (SNP) associated with autoimmune disease susceptibility, little is known about how the SNP is involved in pathogenesis. Here, we established CD4+ T cells expressing wild-type or G307S DNAM-1 and showed that the costimulatory signal from G307S DNAM-1 induced greater pro-inflammatory cytokine production and cell proliferation than that from wild-type DNAM-1. The G307S mutation also enhanced the recruitment of the tyrosine kinase Lck and augmented tyrosine phosphorylation at residue 322 (Tyr322) of DNAM-1. However, conversion of Tyr322 of DNAM-1 to phenylalanine (Y322F mutation) canceled the enhanced activation of CD4+ T cell transfectants expressing G307S DNAM-1. Adoptive transfer of myelin-antigen-specific CD4+ T cells expressing G307S DNAM-1 into mice exacerbated experimental autoimmune encephalomyelitis compared with the transfer of cells expressing wild-type DNAM-1. These findings suggest that rs763361 is a gain-of-function mutation that enhances DNAM-1-mediated costimulatory signaling for proinflammatory responses.

immunology↗