Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjogren Syndrome

Mathias Kaurstad Morthen; Sara Tellefsen; Stephen M. Richards; Scott M. Lieberman; Raheleh Rahimi Darabad; Wendy R. Kam; David A. Sullivan

doi:10.1167/iovs.19-26815

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Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjogren Syndrome

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Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjogren Syndrome

Mathias Kaurstad Morthen, Sara Tellefsen, Stephen M. Richards, Scott M. Lieberman, Raheleh Rahimi Darabad, Wendy R. Kam and David A. Sullivan

Investigative ophthalmology & visual science, Vol.60(6), pp.2181-2197

05/01/2019

DOI: 10.1167/iovs.19-26815

PMCID: PMC6528840

PMID: 31108549

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Abstract

PURPOSE. Sjogren syndrome is an autoimmune disorder that occurs almost exclusively in women and is associated with extensive inflammation in lacrimal tissue, an immune-mediated destruction and/or dysfunction of glandular epithelial cells, and a significant decrease in aqueous tear secretion. We discovered that androgens suppress the inflammation in, and enhance the function of, lacrimal glands in female mouse models (e.g., MRL/MpJ-Tnfrsf6(lpr) [MRL/lpr]) of Sjogren syndrome. In contrast, others have reported that androgens induce an anomalous immunopathology in lacrimal glands of nonobese diabetic/LtJ (NOD) mice. We tested our hypothesis that these hormone actions reflect unique, strain- and tissue-specific effects, which involve significant changes in the expression of immune-related glandular genes. METHODS. Lacrimal glands were obtained from age-matched, adult, female MRL/lpr and NOD mice after treatment with vehicle or testosterone for up to 3 weeks. Tissues were processed for analysis of differentially expressed mRNAs using CodeLink Bioarrays and Affymetrix GeneChips. Data were analyzed with bioinformatics and statistical software. RESULTS. Testosterone significantly influenced the expression of numerous immune-related genes, ontologies, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in lacrimal glands of MRL/lpr and NOD mice. The nature of this hormone-induced immune response was dependent upon the autoimmune strain, and was not duplicated within lacrimal tissues of nonautoimmune BALB/c mice. The majority of immune-response genes regulated by testosterone were of the inflammatory type. CONCLUSIONS. Our findings support our hypothesis and indicate a major role for the lacrimal gland microenvironment in mediating androgen effects on immune gene expression.

Life Sciences & Biomedicine

Ophthalmology

Science & Technology

Details

Title: Subtitle: Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjogren Syndrome
Creators: Mathias Kaurstad Morthen - Oslo University Hospital
Sara Tellefsen - Oslo University Hospital
Stephen M. Richards - The University of Adelaide
Scott M. Lieberman - Univ Iowa, Stead Family Dept Pediat, Carver Coll Med, Iowa City, IA USA
Raheleh Rahimi Darabad - Indiana University
Wendy R. Kam - Harvard University
David A. Sullivan - Harvard University
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.60(6), pp.2181-2197
DOI: 10.1167/iovs.19-26815
PMID: 31108549
PMCID: PMC6528840
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: Assoc Research Vision Ophthalmology Inc
Number of pages: 17
Grant note: NIH EY05612 / National Institutes of Health (Bethesda, MD, USA); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA David A. Sullivan laboratory fund Ocular Surface Research fund
Language: English
Date published: 05/01/2019
Academic Unit: Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
Record Identifier: 9984353937202771

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