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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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. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0184781</identifier><identifier>PMID: 28902875</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2017-09, Vol.12 (9), p.e0184781-e0184781</ispartof><rights>2017 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Meng et al 2017 Meng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-b3cee7488555960bf1d4ede87767b3f4a6194727cd700e860b70ff0458e37ab43</citedby><cites>FETCH-LOGICAL-c552t-b3cee7488555960bf1d4ede87767b3f4a6194727cd700e860b70ff0458e37ab43</cites><orcidid>0000-0001-8195-5703</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597228/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597228/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28902875$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Shiku, Hiroshi</contributor><creatorcontrib>Meng, Zhen</creatorcontrib><creatorcontrib>Klinngam, Wannita</creatorcontrib><creatorcontrib>Edman, Maria C</creatorcontrib><creatorcontrib>Hamm-Alvarez, Sarah F</creatorcontrib><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</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Acinar cells</subject><subject>Animals</subject><subject>Antigen presentation</subject><subject>Antigen Presentation - drug effects</subject><subject>Autoimmune diseases</subject><subject>Biology and Life Sciences</subject><subject>Carbachol</subject><subject>Cathepsin S</subject><subject>Cathepsins - metabolism</subject><subject>Cells, Cultured</subject><subject>Cornea</subject><subject>Cornea - drug effects</subject><subject>Cornea - metabolism</subject><subject>Cornea - pathology</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Diabetes</subject><subject>Epithelial cells</subject><subject>Eye diseases</subject><subject>Glands</subject><subject>Histocompatibility Antigens - metabolism</subject><subject>Histocompatibility Antigens - physiology</subject><subject>Humans</subject><subject>In vitro methods and tests</subject><subject>Inflammation</subject><subject>Interferon</subject><subject>Interferon-gamma - metabolism</subject><subject>Interferon-gamma - pharmacology</subject><subject>Interferon-gamma - physiology</subject><subject>Irritation</subject><subject>Lacrimal Apparatus - drug effects</subject><subject>Lacrimal Apparatus - metabolism</subject><subject>Lacrimal Apparatus - pathology</subject><subject>Lacrimal gland and Nasolacrimal duct</subject><subject>Lymphocytes</subject><subject>Major histocompatibility complex</subject><subject>Major Histocompatibility Complex - immunology</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred NOD</subject><subject>Pain</subject><subject>Pathogenesis</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Pharmacy</subject><subject>Rabbits</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>Salivary glands</subject><subject>Secretion</subject><subject>Sjogren's syndrome</subject><subject>Sjogren's Syndrome - immunology</subject><subject>Sjogren's Syndrome - metabolism</subject><subject>Sjogren's Syndrome - pathology</subject><subject>Studies</subject><subject>Tears</subject><subject>Tumor necrosis factor-TNF</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUstuEzEUHSEQLYU_QGCJBWwSPB7P2LOphMorUkUXgbXl2NdTRx472E6lfhcSHwB7vglPklYtYuGHrs85997jW1XPazyvG1a_XYdt9NLNN8HDHNecMl4_qI7rviGzjuDm4Z37UfUkpTXGbcO77nF1RHiPCWftcfVr4TNEAzH42Z8fKEeQeQSfkfXoyuYYEDirbE4ohRFQMChfAlKX0g-QJpCSJbBJ5bZE0uuysh3Ao02EVHRktsFP-ChVSWRTtmpScVJFO0qHBldYaUdVIXqQCZkYxl2aLxfv0Ri2CcquwU285fr3zyGCf53Q8trrgoSn1SMjXYJnh_Ok-vbxw9ezz7Pzi0-Ls3fnM9W2JM9WjQJglPO2bfsOr0ytKWjgjHVs1Rgqu7qnjDClGcbAC4JhYzBtOTRMrmhzUr3c625cSOJgfxLFZN425Ud4QSz2CB3kWmymBuO1CNKKXSDEQchYDHAgaGdqhjUlBAxVjHNWIrrueat6rnpdtE4P2barEbQqXkbp7onef_H2UgzhSpTuGCFTMW8OAjF830LKYrRJgSt-Q_F0VzdvCcddgb76B_r_7ugepWJIKYK5LabGYhrJG5aYRlIcRrLQXtxt5JZ0M4PNXyYT5JA</recordid><startdate>20170913</startdate><enddate>20170913</enddate><creator>Meng, Zhen</creator><creator>Klinngam, Wannita</creator><creator>Edman, Maria C</creator><creator>Hamm-Alvarez, Sarah F</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-8195-5703</orcidid></search><sort><creationdate>20170913</creationdate><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</title><author>Meng, Zhen ; Klinngam, Wannita ; Edman, Maria C ; Hamm-Alvarez, Sarah F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-b3cee7488555960bf1d4ede87767b3f4a6194727cd700e860b70ff0458e37ab43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acinar cells</topic><topic>Animals</topic><topic>Antigen presentation</topic><topic>Antigen Presentation - drug effects</topic><topic>Autoimmune diseases</topic><topic>Biology and Life Sciences</topic><topic>Carbachol</topic><topic>Cathepsin S</topic><topic>Cathepsins - metabolism</topic><topic>Cells, Cultured</topic><topic>Cornea</topic><topic>Cornea - drug effects</topic><topic>Cornea - metabolism</topic><topic>Cornea - pathology</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Diabetes</topic><topic>Epithelial cells</topic><topic>Eye diseases</topic><topic>Glands</topic><topic>Histocompatibility Antigens - metabolism</topic><topic>Histocompatibility Antigens - physiology</topic><topic>Humans</topic><topic>In vitro methods and tests</topic><topic>Inflammation</topic><topic>Interferon</topic><topic>Interferon-gamma - metabolism</topic><topic>Interferon-gamma - pharmacology</topic><topic>Interferon-gamma - physiology</topic><topic>Irritation</topic><topic>Lacrimal Apparatus - drug effects</topic><topic>Lacrimal Apparatus - metabolism</topic><topic>Lacrimal Apparatus - pathology</topic><topic>Lacrimal gland and Nasolacrimal duct</topic><topic>Lymphocytes</topic><topic>Major histocompatibility complex</topic><topic>Major Histocompatibility Complex - 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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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