BACKGROUND: Interleukin (IL)-4 is a pleiotropic cytokine that plays an important role in the pathogenesis of the allergic inflammation and asthma. Upon IL-4 receptor (IL-4R) engagement, a variety of signaling mediators, such as JAK kinases and STAT-6 are activated, leading to induction of IL-4 target gene expression including CD23 and germline C epsilon transcription. The function of a membrane-proximal domain of IL-4Ra, termed ID-1, remains to be characterized to date. OBJECTIVE: To assess whether the ID-1 domain mediates the induction of IL-4 target gene expression in a STAT-6-dependent manner. METHODS: The intracellular region of IL-4Ralpha was translationally fused to the extracellular region of IL-2Rbeta to provide ligand specificity to IL-2. Acidic amino acids and serine residues in the ID-1 domain of the chimeric receptor were substituted by site-directed mutagenesis. These receptor cDNAs were stably transfected to M12.4.1 murine B lymphoma cells. Following IL-2 stimulation, wild type and mutant clones for the ID-1 motif were subjected to FACS. RNA blotting and elecroporetic mobility shift assays to address the levels of CD23, germline C epsilon and STAT-6 inductions, respectively. RESULTS: ID-1 mutant clones were defective in gene induction of CD23 and germline C epsilon in response to IL-2 stimulation, as compared with wildtype clones. Moreover, IL-2-mediated STAT-6 activation was abolished in ID-1 mutant clones. CONCLUSION: These results demonstrate that the ID-1 domain of IL-4Ra is essential to induce IL-4 target gene expression through a STAT-6-dependent pathway.
Amino Acids, Acidic ; Asthma ; Clone Cells ; DNA, Complementary ; Electrophoretic Mobility Shift Assay ; Gene Expression ; Inflammation ; Interleukin-2 ; Interleukin-4 Receptor alpha Subunit* ; Interleukin-4* ; Interleukins ; Janus Kinases ; Lymphoma ; Mutagenesis, Site-Directed ; Receptors, Interleukin-4 ; RNA ; Sensitivity and Specificity ; Serine

OBJECTIVES: Occupational stress management is particularly important for successful business operations, since occupational stress adversely affects workers’ health, eventually lowering their productivity. Therefore, this study aimed to investigate the correlation between occupational stress and health-related productivity loss (HRPL) among Korean workers. METHODS: In 2021, 1,078 workers participated in a web-based questionnaire survey. HRPL was measured using the Work Productivity and Activity Impairment Questionnaire, and occupational stress was measured using the Korean Occupational Stress Scale-Short Form. The occupational stress level was divided into tertiles (low, intermediate, and high), and the low occupational stress group was used as the reference group. Using a generalised linear model, differences in labour productivity loss according to the level of occupational stress were tested after adjusting for demographic characteristics such as age, gender, education level, household income, occupation, and underlying medical conditions. RESULTS: Non-parametric regression analysis of HRPL according to occupational stress showed a direct association between occupational stress and HRPL. A statistically significant difference was observed in HRPL between participants with intermediate and high occupational stress and those with low occupational stress. CONCLUSIONS Our results support the hypothesis that high occupational stress is associated with decreased labour productivity.