Combined Repetitive Inhalant Endotoxin and Collagen-Induced Arthritis Drive Inflammatory Lung Disease and Arthritis Severity in a Testosterone-Dependent Manner

Details

• Personal Author:
  Duryee MJ ; England BR ; Gaurav R ; Gleason A ; Hunter CD ; Mikuls TR ; Nelson AJ ; Poole JA ; Ramler E ; Schwab AD ; Thiele GM ; Wyatt TA
• Description:
  Respiratory-related diseases are a leading cause of death in rheumatoid arthritis (RA) and are disproportionately higher in men, which may be attributable to environmental risk factors. Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung disease with a combination of airborne exposures and collagen-induced arthritis (CIA). This study aimed to determine whether hormone-dependent differences explained these observations. Arthritis-prone male intact and castrated DBA/1J mice received intranasal inhalation of lipopolysaccharide (LPS) daily for 5 wk and CIA induction. Arthritis scores and serum pentraxin-2 levels were increased in castrated versus intact mice. In contrast, airway cell influx, lung tissue infiltrates, and lung levels of proinflammatory and profibrotic markers (C5a, IL-33, and matrix metalloproteinases) were reduced in castrated versus intact mice. CIA + LPS-induced lung histopathology changes and the expression of lung autoantigens including malondialdehyde acetaldehyde (MAA)- and citrulline (CIT)-modified proteins and vimentin were reduced in castrated animals. There were no differences in serum anti-MAA or anti-CIT protein antibody (ACPA) levels or serum pentraxin levels between groups. Testosterone replacement led to a reversal of several lung inflammatory/profibrotic endpoints noted earlier in castrated male CIA + LPS-treated mice with testosterone supplementation promoting neutrophil influx, MAA expression, and TNF-a, IL-6, and MMP-9. These findings imply that testosterone contributes to lung and arthritis inflammatory responses following CIA + LPS coexposure, but not to systemic autoantibody responses. The CIA + LPS model provides a paradigm for investigations focused on the mechanistic underpinnings for epidemiologic and phenotypic sex differences in RA-related lung disease. [Description provided by NIOSH]
• Subjects:
  Endotoxins Immune System Laboratories Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Sex Characteristics
• Keywords:
  Author Keywords: Autoimmunity Autoimmune Diseases Histopathology Immune Reaction Inflammation Inhalation Interstitial Lung Disease Laboratory Animals Lung Disease Rheumatoid Disorders Sex Differences Sex Factors Testosterone

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  326
• Issue:
  3
• NIOSHTIC Number:
  nn:20068974
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2024 Mar; 326(3):L239-L251
• Contact Point Address:
  Jill A. Poole, Division of Allergy & Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fd58d36cd652b21e7c330f2ff7e746a8ebd481e5680e255db2988c354151a00854e35ac16fc74b605139660c45e2b3c0891fbcd7e612936fbcc43467c00fe556
• Download URL:
  https://stacks.cdc.gov/view/cdc/207531/cdc_207531_DS1.pdf
• File Type:
  [PDF - 3.08 MB ]