Interferon-γ treatment in vitro elicits some of the changes in cathepsin S and antigen presentation characteristic of lacrimal glands and corneas from the NOD mouse model of Sjögren's Syndrome

Inflammation and impaired secretion by lacrimal and salivary glands are hallmarks of the autoimmune disease, Sjögren's Syndrome. These changes in the lacrimal gland promote dryness and inflammation of the ocular surface, causing pain, irritation and corneal damage. The changes that initiate and...

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Veröffentlicht in:PloS one 2017-09, Vol.12 (9), p.e0184781-e0184781
Hauptverfasser: Meng, Zhen, Klinngam, Wannita, Edman, Maria C, Hamm-Alvarez, Sarah F
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Klinngam, Wannita
Edman, Maria C
Hamm-Alvarez, Sarah F
description Inflammation and impaired secretion by lacrimal and salivary glands are hallmarks of the autoimmune disease, Sjögren's Syndrome. These changes in the lacrimal gland promote dryness and inflammation of the ocular surface, causing pain, irritation and corneal damage. The changes that initiate and sustain autoimmune inflammation in the lacrimal gland are not well-established. Here we demonstrate that interferon-γ (IFN-γ) is significantly elevated in lacrimal gland and tears of the male NOD mouse, a model of autoimmune dacryoadenitis which exhibits many ocular characteristics of Sjögren's Syndrome, by 12 weeks of age early in lacrimal gland inflammation. Working either with primary cultured lacrimal gland acinar cells from BALB/c mice and/or rabbits, in vitro IFN-γ treatment for 48 hr decreased expression of Rab3D concurrent with increased expression of cathepsin S. Although total cellular cathepsin S activity was not commensurately increased, IFN-γ treated lacrimal gland acinar cells showed a significant increase in carbachol-stimulated secretion of cathepsin S similar to the lacrimal gland in disease. In vitro IFN-γ treatment did not increase the expression of most components of major histocompatibility complex (MHC) class II-mediated antigen presentation although antigen presentation was slightly but significantly stimulated in primary cultured lacrimal gland acinar cells. However, exposure of cultured human corneal epithelial cells to IFN-γ more robustly increased expression and activity of cathepsin S in parallel with increased expression and function of MHC class II-mediated antigen presentation. We propose that early elevations in IFN-γ contribute to specific features of ocular disease pathology in Sjögren's Syndrome.
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These changes in the lacrimal gland promote dryness and inflammation of the ocular surface, causing pain, irritation and corneal damage. The changes that initiate and sustain autoimmune inflammation in the lacrimal gland are not well-established. Here we demonstrate that interferon-γ (IFN-γ) is significantly elevated in lacrimal gland and tears of the male NOD mouse, a model of autoimmune dacryoadenitis which exhibits many ocular characteristics of Sjögren's Syndrome, by 12 weeks of age early in lacrimal gland inflammation. Working either with primary cultured lacrimal gland acinar cells from BALB/c mice and/or rabbits, in vitro IFN-γ treatment for 48 hr decreased expression of Rab3D concurrent with increased expression of cathepsin S. Although total cellular cathepsin S activity was not commensurately increased, IFN-γ treated lacrimal gland acinar cells showed a significant increase in carbachol-stimulated secretion of cathepsin S similar to the lacrimal gland in disease. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meng, Zhen</au><au>Klinngam, Wannita</au><au>Edman, Maria C</au><au>Hamm-Alvarez, Sarah F</au><au>Shiku, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interferon-γ treatment in vitro elicits some of the changes in cathepsin S and antigen presentation characteristic of lacrimal glands and corneas from the NOD mouse model of Sjögren's Syndrome</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-09-13</date><risdate>2017</risdate><volume>12</volume><issue>9</issue><spage>e0184781</spage><epage>e0184781</epage><pages>e0184781-e0184781</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Inflammation and impaired secretion by lacrimal and salivary glands are hallmarks of the autoimmune disease, Sjögren's Syndrome. These changes in the lacrimal gland promote dryness and inflammation of the ocular surface, causing pain, irritation and corneal damage. The changes that initiate and sustain autoimmune inflammation in the lacrimal gland are not well-established. Here we demonstrate that interferon-γ (IFN-γ) is significantly elevated in lacrimal gland and tears of the male NOD mouse, a model of autoimmune dacryoadenitis which exhibits many ocular characteristics of Sjögren's Syndrome, by 12 weeks of age early in lacrimal gland inflammation. Working either with primary cultured lacrimal gland acinar cells from BALB/c mice and/or rabbits, in vitro IFN-γ treatment for 48 hr decreased expression of Rab3D concurrent with increased expression of cathepsin S. Although total cellular cathepsin S activity was not commensurately increased, IFN-γ treated lacrimal gland acinar cells showed a significant increase in carbachol-stimulated secretion of cathepsin S similar to the lacrimal gland in disease. In vitro IFN-γ treatment did not increase the expression of most components of major histocompatibility complex (MHC) class II-mediated antigen presentation although antigen presentation was slightly but significantly stimulated in primary cultured lacrimal gland acinar cells. However, exposure of cultured human corneal epithelial cells to IFN-γ more robustly increased expression and activity of cathepsin S in parallel with increased expression and function of MHC class II-mediated antigen presentation. We propose that early elevations in IFN-γ contribute to specific features of ocular disease pathology in Sjögren's Syndrome.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28902875</pmid><doi>10.1371/journal.pone.0184781</doi><orcidid>https://orcid.org/0000-0001-8195-5703</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acinar cells
Animals
Antigen presentation
Antigen Presentation - drug effects
Autoimmune diseases
Biology and Life Sciences
Carbachol
Cathepsin S
Cathepsins - metabolism
Cells, Cultured
Cornea
Cornea - drug effects
Cornea - metabolism
Cornea - pathology
Cytokines
Dendritic cells
Diabetes
Epithelial cells
Eye diseases
Glands
Histocompatibility Antigens - metabolism
Histocompatibility Antigens - physiology
Humans
In vitro methods and tests
Inflammation
Interferon
Interferon-gamma - metabolism
Interferon-gamma - pharmacology
Interferon-gamma - physiology
Irritation
Lacrimal Apparatus - drug effects
Lacrimal Apparatus - metabolism
Lacrimal Apparatus - pathology
Lacrimal gland and Nasolacrimal duct
Lymphocytes
Major histocompatibility complex
Major Histocompatibility Complex - immunology
Male
Medicine and Health Sciences
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Pain
Pathogenesis
Pharmaceutical sciences
Pharmacology
Pharmacy
Rabbits
Research and Analysis Methods
Rodents
Salivary glands
Secretion
Sjogren's syndrome
Sjogren's Syndrome - immunology
Sjogren's Syndrome - metabolism
Sjogren's Syndrome - pathology
Studies
Tears
Tumor necrosis factor-TNF
title Interferon-γ treatment in vitro elicits some of the changes in cathepsin S and antigen presentation characteristic of lacrimal glands and corneas from the NOD mouse model of Sjögren's Syndrome
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