Occupational health effect of TCE exposure: Experiment evidence of gene-environment interaction in hypersensitivity reaction.
Chem Biol Interact
; 368: 110220, 2022 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-36243146
ABSTRACT
BACKGROUND:
Recently, Trichloroethylene (TCE) induced TCE hypersensitivity syndrome (THS) has attracted the attention of many researchers in the field of environmental and occupational health. Studies have revealed that Human leukocyte antigen (HLA) polymorphisms were the important genetic determinants of the diseases, but the potential molecular mechanism remains unclear.OBJECTIVE:
This study aimed to investigate the association between THS and HLA at the molecular level.METHOD:
We chose the human B-lymphoblastoid cell line Hmy2.C1R transfected with cDNA of HLA-B*1301 and HLA-B*1302 to analyze the characteristics of HLA-B-binding peptides and investigate the effect of TCE on the binding affinity of peptides to the HLA-B molecules. Further, the mathematical model was used to identify the possible interaction between TCE and HLA-B*1301 or HLA-B*1302 molecule.RESULTS:
54 HLA-B*1301-binding peptides and 85 HLA-B*1302-binding peptides were identified. Comparing the protein sequences of HLA-B*1301 and HLA-B*1302, amino acids were different at positions 94, 95 and 97. The results of the binding affinity of self-peptides to HLA molecules in the presence of TCE showed that TCE significantly decreased the binding affinity of peptides to HLA-B*1301 only, but did not affect that of HLA-B*1302. Molecular docking model showed that there was a unique high-affinity binding mode between TCE and HLA-B*1301 (but not HLA-B*1302), and the binding site located in the region of F pocket, suggesting that the unique structure of the F pocket of HLA-B*1301 might provide the possibility of binding TCE. The pathogenesis of interaction between HLA-B*1301 and TCE might belong to the model of the alteration of the HLA-presented self-peptide repertoire.DISCUSSION:
This study explored the molecular mechanism of the association between THS and HLA-B*1301, and had important implications for understanding the role of gene-environment interaction in the development of complex environment-related diseases.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tricloroetileno
/
Salud Laboral
/
Hipersensibilidad
Tipo de estudio:
Prognostic_studies
Aspecto:
Determinantes_sociais_saude
Límite:
Humans
Idioma:
En
Revista:
Chem Biol Interact
Año:
2022
Tipo del documento:
Article
País de afiliación:
China