Proteomic Profiling Reveals Immunologic Mediators of Endotoxin-Related Lung Function Decline: A Longitudinal Prospective Study in Textile Workers

Details

• Journal Article:
  Respiratory Research
• Personal Author:
  Wang, Hantao ; Goodney, Gabriel ; Zhang, Fengying ; Lai, Peggy S. ; Su, Li ; Gao, Peng ; Lim, Jungeun ; Lo, Shelton ; Liu, Zhonghua ; Christiani, David C. ; Wong, Jason Y. Y.
• Description:
  Background: Endotoxin is a major pathogenic component of cotton dust in the textile industry. While airborne endotoxin is associated with lung function decline, the underlying molecular mechanisms remain unclear. Proteomic profiling could provide important insights into the pathways that drive the harmful respiratory effects of endotoxin. Methods: We conducted serum proteomic profiling of 221 endotoxin-exposed cotton workers and 192 endotoxin-free silk workers from the longitudinal cohort of the Shanghai Textile Worker Study. Using blood samples collected in 2016, proteins were quantified by data-independent acquisition mass spectrometry and genotyping was assessed using low-pass whole genome sequencing. Forced expiratory volume in 1 s (FEV-1) was measured in 2011 and 2016. We used adjusted regression to identify differentially expressed proteins (DEPs) between the exposed and control groups. Causal mediation analyses were performed to identify protein mediators. Mendelian Randomization (MR) analyses provided causal estimates of protein effects on lung function change. Results: Among 2,962 quantified proteins, we identified 224 proteins that were differentially expressed between cotton and silk workers (Bonferroni p < 0.05). Top enriched pathways associated with DEPs were the complement and coagulation cascades (KEGG: hsa04610) and the chemokine signaling pathway (KEGG: hsa04062). Adaptive immune proteins collectively mediated endotoxin-related lung function decline (binomial p = 9.63 × 10??7). Two immunoglobulin domain proteins significantly (Bonferroni p < 0.05) mediated endotoxin effects on lung function change: Epididymis luminal protein 180 (HEL180) and IGL c3728_light_IGKV4-1_IGKJ1 (IGL c3728), with 46.4% (p = 0.04) and 46.9% (p = 0.05) proportion of the total effect that was mediated. MR estimates demonstrated that every 2-fold decrease in HEL180 and IGL c3728 expression was associated with an FEV-1 decline of 1.90 ml/year (95% CI: [0.79, 3.02]) and 2.36 ml/year (95% CI: [1.68, 3.02]), respectively. Conclusion: Using a trans-omic approach, our findings suggest that chronic endotoxin exposure suppresses immunoglobulin domain proteins, weakens adaptive immunity, and accelerates lung function decline. These findings provide greater precision in understanding biological mechanisms underlying endotoxin-related respiratory dysfunction.
• Subjects:
  Dust Endotoxins Lung Occupational Health Respiratory System Safety Textile Industry
• Keywords:
  Author Keywords: Cotton Dust; Occupational Health; Occupational Epidemiology; Vegetable Dust Textile Workers; Endotoxins; Longitudinal Study; Lung Function; Proteins; Immune Reaction; Molecular Biology; Cohort Studies; Chronic Exposure; Epidemiology; Dust Exposure; Organic Dusts;
• Source:
  Respir Res 2026 Apr; :[Epub ahead of print]
• ISSN:
  1465-9921
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; Maryland ; New York ; Boston Region [OSHA] ; Philadelphia Region [OSHA] ; New York Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  34 pdf pages
• NIOSHTIC Number:
  nn:20071469
• Contact Point Address:
  Jason Y. Y. Wong, Epidemiology and Community Health Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA
• Email:
  Jason.wong@nih.gov
• Federal Fiscal Year:
  2026
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:879833aea68729e2008d4445fc4dd6ccbb488e5e314100a441df89d3923bfdfa4da6dcbf8c73107535125872863491c5e64d4fd0cac85a8942ea663727ed889b
• Download URL:
  https://stacks.cdc.gov/view/cdc/259067/cdc_259067_DS1.pdf
• File Type:
  [PDF - 1.36 MB ]