IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in patients with immunoglobulin G4–related disease
Summary Immunoglobulin (Ig) G4–related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 concentrations, infiltration of IgG4-positive plasmacytes, and fibrosis of various organs. Several groups have reported that IgG4-RD is a unique inflammatory disorder characterized by an...
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| Veröffentlicht in: | Human pathology 2015-12, Vol.46 (12), p.1850-1858 |
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| creator | Komori, Takeshi, MD Kondo, Satoru, MD, PhD Wakisaka, Naohiro, MD, PhD Nakanishi, Yosuke, MD, PhD Nakanishi-Yagi, Sayaka, MD, PhD Tsuji, Akira, MD, PhD Endo, Kazuhira, MD, PhD Murono, Shigeyuki, MD, PhD Yoshizaki, Tomokazu, MD, PhD |
| description | Summary Immunoglobulin (Ig) G4–related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 concentrations, infiltration of IgG4-positive plasmacytes, and fibrosis of various organs. Several groups have reported that IgG4-RD is a unique inflammatory disorder characterized by an immune reaction predominantly mediated by T helper (Th) 2 and regulatory T cells. Meanwhile, recent studies have demonstrated that interleukin (IL) 18 has a potential to trigger the production of Th2 cytokines by Th1 cells. We analyzed IL-18 expression in submandibular glands of patients with IgG4-RD (20 cases) and controls (19 cases) by immunohistochemical analysis and quantitative real-time reverse-transcription polymerase chain reaction. We found that IL-18 was highly expressed in submandibular glands of patients with IgG4-RD than in controls with both protein ( P < .05, χ2 test) and messenger RNA levels ( P < .05, Mann-Whitney U test). In addition, the expression of IL-18 and IL-13 was correlated in submandibular glands of patients with IgG4-RD. Moreover, by analyzing dual immunofluorescence staining, a few numbers of cells were double positive for IL-13 and interferon γ at the inflammatory infiltrates of submandibular glands of patients with IgG4-RD. These data suggest a possibility that IL-13 is produced by Th1 cells. We speculated that IL-18 stimulates Th1 cells producing Th2 cytokines and enhances the immune reaction of Th2 cytokines in pathogenesis of IgG4-RD. |
| doi_str_mv | 10.1016/j.humpath.2015.08.002 |
| format | Article |
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Several groups have reported that IgG4-RD is a unique inflammatory disorder characterized by an immune reaction predominantly mediated by T helper (Th) 2 and regulatory T cells. Meanwhile, recent studies have demonstrated that interleukin (IL) 18 has a potential to trigger the production of Th2 cytokines by Th1 cells. We analyzed IL-18 expression in submandibular glands of patients with IgG4-RD (20 cases) and controls (19 cases) by immunohistochemical analysis and quantitative real-time reverse-transcription polymerase chain reaction. We found that IL-18 was highly expressed in submandibular glands of patients with IgG4-RD than in controls with both protein ( P < .05, χ2 test) and messenger RNA levels ( P < .05, Mann-Whitney U test). In addition, the expression of IL-18 and IL-13 was correlated in submandibular glands of patients with IgG4-RD. Moreover, by analyzing dual immunofluorescence staining, a few numbers of cells were double positive for IL-13 and interferon γ at the inflammatory infiltrates of submandibular glands of patients with IgG4-RD. These data suggest a possibility that IL-13 is produced by Th1 cells. We speculated that IL-18 stimulates Th1 cells producing Th2 cytokines and enhances the immune reaction of Th2 cytokines in pathogenesis of IgG4-RD.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2015.08.002</identifier><identifier>PMID: 26433704</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Asthma ; Cytokines ; Disease ; Female ; Hospitals ; Humans ; IFN-γ ; IgG4-RD ; IL-13 ; IL-18 ; Immune System Diseases - immunology ; Immunoglobulin G - immunology ; Immunoglobulins ; Immunohistochemistry ; Interleukin-18 - biosynthesis ; Interleukin-18 - immunology ; Laboratories ; Male ; Males ; Middle Aged ; Otolaryngology ; Pathogenesis ; Pathology ; Patients ; Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; Salivary glands ; Studies ; Submandibular Gland - immunology ; Submandibular Gland - pathology ; Th1 Cells - immunology</subject><ispartof>Human pathology, 2015-12, Vol.46 (12), p.1850-1858</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Dec 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c598t-e9bc174affc9d9dfdcc57594bc6b45e2f1bace4b06b18a6f1b9516f46755e1f03</citedby><cites>FETCH-LOGICAL-c598t-e9bc174affc9d9dfdcc57594bc6b45e2f1bace4b06b18a6f1b9516f46755e1f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817715003068$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26433704$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Komori, Takeshi, MD</creatorcontrib><creatorcontrib>Kondo, Satoru, MD, PhD</creatorcontrib><creatorcontrib>Wakisaka, Naohiro, MD, PhD</creatorcontrib><creatorcontrib>Nakanishi, Yosuke, MD, PhD</creatorcontrib><creatorcontrib>Nakanishi-Yagi, Sayaka, MD, PhD</creatorcontrib><creatorcontrib>Tsuji, Akira, MD, PhD</creatorcontrib><creatorcontrib>Endo, Kazuhira, MD, PhD</creatorcontrib><creatorcontrib>Murono, Shigeyuki, MD, PhD</creatorcontrib><creatorcontrib>Yoshizaki, Tomokazu, MD, PhD</creatorcontrib><title>IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in patients with immunoglobulin G4–related disease</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary Immunoglobulin (Ig) G4–related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 concentrations, infiltration of IgG4-positive plasmacytes, and fibrosis of various organs. Several groups have reported that IgG4-RD is a unique inflammatory disorder characterized by an immune reaction predominantly mediated by T helper (Th) 2 and regulatory T cells. Meanwhile, recent studies have demonstrated that interleukin (IL) 18 has a potential to trigger the production of Th2 cytokines by Th1 cells. We analyzed IL-18 expression in submandibular glands of patients with IgG4-RD (20 cases) and controls (19 cases) by immunohistochemical analysis and quantitative real-time reverse-transcription polymerase chain reaction. We found that IL-18 was highly expressed in submandibular glands of patients with IgG4-RD than in controls with both protein ( P < .05, χ2 test) and messenger RNA levels ( P < .05, Mann-Whitney U test). In addition, the expression of IL-18 and IL-13 was correlated in submandibular glands of patients with IgG4-RD. Moreover, by analyzing dual immunofluorescence staining, a few numbers of cells were double positive for IL-13 and interferon γ at the inflammatory infiltrates of submandibular glands of patients with IgG4-RD. These data suggest a possibility that IL-13 is produced by Th1 cells. We speculated that IL-18 stimulates Th1 cells producing Th2 cytokines and enhances the immune reaction of Th2 cytokines in pathogenesis of IgG4-RD.</description><subject>Adult</subject><subject>Aged</subject><subject>Asthma</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Female</subject><subject>Hospitals</subject><subject>Humans</subject><subject>IFN-γ</subject><subject>IgG4-RD</subject><subject>IL-13</subject><subject>IL-18</subject><subject>Immune System Diseases - immunology</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulins</subject><subject>Immunohistochemistry</subject><subject>Interleukin-18 - biosynthesis</subject><subject>Interleukin-18 - immunology</subject><subject>Laboratories</subject><subject>Male</subject><subject>Males</subject><subject>Middle Aged</subject><subject>Otolaryngology</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Patients</subject><subject>Proteins</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Salivary glands</subject><subject>Studies</subject><subject>Submandibular Gland - immunology</subject><subject>Submandibular Gland - pathology</subject><subject>Th1 Cells - immunology</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNksFu1DAQhiMEokvhEUCWuHBJGCe2k1xAVVVKpZU4AGfLsccbL85msRNgbxWvwBvyJDjaBaReQLJkj_zN75n5nWVPKRQUqHi5Lfp52KupL0qgvICmACjvZSvKqzJvqra8n60AmMgbWtdn2aMYtwCUcsYfZmelYFVVA1tl32_WOW2Ii6R3m94fCH7bB4wRDXG7tKxXw6CmMRyWwPkpqAkjGS2JczeonXHd7FUgG5_OcclJNTncTZF8dVNP3DDMu3Hjx4Sly2v28_ZHQJ9EDDEuoor4OHtglY_45LSfZx_fXH24fJuv313fXF6sc83bZsqx7TStmbJWt6Y11mjNa96yTouOcSwt7ZRG1oHoaKNECltOhWWi5hypheo8e3HU3Yfx84xxkoOLGn2qHMc5SlpzWqbxcf4faMXKBnhdJfT5HXQ7zmGXGlmoZAYDIRLFj5QOY4wBrdwHN6hwkBTk4qfcypOfcvFTQiOTnynv2Uk9TRvNn6zfBibg9RHANLkvDoOMOo1fo3EB9STN6P75xKs7Cjo55bTyn_CA8W83MpYS5PvlUy1_inKACkRT_QKyYMum</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Komori, Takeshi, MD</creator><creator>Kondo, Satoru, MD, PhD</creator><creator>Wakisaka, Naohiro, MD, PhD</creator><creator>Nakanishi, Yosuke, MD, PhD</creator><creator>Nakanishi-Yagi, Sayaka, MD, PhD</creator><creator>Tsuji, Akira, MD, PhD</creator><creator>Endo, Kazuhira, MD, PhD</creator><creator>Murono, Shigeyuki, MD, PhD</creator><creator>Yoshizaki, Tomokazu, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>K9.</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20151201</creationdate><title>IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in patients with immunoglobulin G4–related disease</title><author>Komori, Takeshi, MD ; Kondo, Satoru, MD, PhD ; Wakisaka, Naohiro, MD, PhD ; Nakanishi, Yosuke, MD, PhD ; Nakanishi-Yagi, Sayaka, MD, PhD ; Tsuji, Akira, MD, PhD ; Endo, Kazuhira, MD, PhD ; Murono, Shigeyuki, MD, PhD ; Yoshizaki, Tomokazu, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c598t-e9bc174affc9d9dfdcc57594bc6b45e2f1bace4b06b18a6f1b9516f46755e1f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Asthma</topic><topic>Cytokines</topic><topic>Disease</topic><topic>Female</topic><topic>Hospitals</topic><topic>Humans</topic><topic>IFN-γ</topic><topic>IgG4-RD</topic><topic>IL-13</topic><topic>IL-18</topic><topic>Immune System Diseases - immunology</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulins</topic><topic>Immunohistochemistry</topic><topic>Interleukin-18 - biosynthesis</topic><topic>Interleukin-18 - immunology</topic><topic>Laboratories</topic><topic>Male</topic><topic>Males</topic><topic>Middle Aged</topic><topic>Otolaryngology</topic><topic>Pathogenesis</topic><topic>Pathology</topic><topic>Patients</topic><topic>Proteins</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Salivary glands</topic><topic>Studies</topic><topic>Submandibular Gland - immunology</topic><topic>Submandibular Gland - pathology</topic><topic>Th1 Cells - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Komori, Takeshi, MD</creatorcontrib><creatorcontrib>Kondo, Satoru, MD, PhD</creatorcontrib><creatorcontrib>Wakisaka, Naohiro, MD, PhD</creatorcontrib><creatorcontrib>Nakanishi, Yosuke, MD, PhD</creatorcontrib><creatorcontrib>Nakanishi-Yagi, Sayaka, MD, PhD</creatorcontrib><creatorcontrib>Tsuji, Akira, MD, PhD</creatorcontrib><creatorcontrib>Endo, Kazuhira, MD, PhD</creatorcontrib><creatorcontrib>Murono, Shigeyuki, MD, PhD</creatorcontrib><creatorcontrib>Yoshizaki, Tomokazu, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Komori, Takeshi, MD</au><au>Kondo, Satoru, MD, PhD</au><au>Wakisaka, Naohiro, MD, PhD</au><au>Nakanishi, Yosuke, MD, PhD</au><au>Nakanishi-Yagi, Sayaka, MD, PhD</au><au>Tsuji, Akira, MD, PhD</au><au>Endo, Kazuhira, MD, PhD</au><au>Murono, Shigeyuki, MD, PhD</au><au>Yoshizaki, Tomokazu, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in patients with immunoglobulin G4–related disease</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>46</volume><issue>12</issue><spage>1850</spage><epage>1858</epage><pages>1850-1858</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Summary Immunoglobulin (Ig) G4–related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 concentrations, infiltration of IgG4-positive plasmacytes, and fibrosis of various organs. Several groups have reported that IgG4-RD is a unique inflammatory disorder characterized by an immune reaction predominantly mediated by T helper (Th) 2 and regulatory T cells. Meanwhile, recent studies have demonstrated that interleukin (IL) 18 has a potential to trigger the production of Th2 cytokines by Th1 cells. We analyzed IL-18 expression in submandibular glands of patients with IgG4-RD (20 cases) and controls (19 cases) by immunohistochemical analysis and quantitative real-time reverse-transcription polymerase chain reaction. We found that IL-18 was highly expressed in submandibular glands of patients with IgG4-RD than in controls with both protein ( P < .05, χ2 test) and messenger RNA levels ( P < .05, Mann-Whitney U test). In addition, the expression of IL-18 and IL-13 was correlated in submandibular glands of patients with IgG4-RD. Moreover, by analyzing dual immunofluorescence staining, a few numbers of cells were double positive for IL-13 and interferon γ at the inflammatory infiltrates of submandibular glands of patients with IgG4-RD. These data suggest a possibility that IL-13 is produced by Th1 cells. We speculated that IL-18 stimulates Th1 cells producing Th2 cytokines and enhances the immune reaction of Th2 cytokines in pathogenesis of IgG4-RD.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26433704</pmid><doi>10.1016/j.humpath.2015.08.002</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Asthma Cytokines Disease Female Hospitals Humans IFN-γ IgG4-RD IL-13 IL-18 Immune System Diseases - immunology Immunoglobulin G - immunology Immunoglobulins Immunohistochemistry Interleukin-18 - biosynthesis Interleukin-18 - immunology Laboratories Male Males Middle Aged Otolaryngology Pathogenesis Pathology Patients Proteins Reverse Transcriptase Polymerase Chain Reaction Salivary glands Studies Submandibular Gland - immunology Submandibular Gland - pathology Th1 Cells - immunology |
| title | IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in patients with immunoglobulin G4–related disease |
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