The P2X7 receptor–inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome
Objective Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7R)–NLRP3 inflammasome complex modulates the release of the inflammatory cytokines IL‐1β and IL‐18. The presence of P2X7R in salivary glands sugges...
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| Veröffentlicht in: | Journal of internal medicine 2013-11, Vol.274 (5), p.480-489 |
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| creator | Baldini, C. Rossi, C. Ferro, F. Santini, E. Seccia, V. Donati, V. Solini, A. |
| description | Objective
Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7R)–NLRP3 inflammasome complex modulates the release of the inflammatory cytokines IL‐1β and IL‐18. The presence of P2X7R in salivary glands suggests an interesting scenario for the initiation and amplification of the innate immune response in pSS. Therefore, the aim of this study was to assess the role of the P2X7R–NLRP3 inflammasome in pSS.
Subjects and Methods
Twenty‐one consecutive patients with pSS according to the American–European Consensus Group criteria and 15 patients with sicca syndrome (i.e. without Sjögren's syndrome, non‐SS) were enrolled in this study, together with six control (CTL) subjects. Expression of the P2X7R‐NLRP3 platform and IL‐18 was determined by real‐time PCR and western blotting in gland specimens and peripheral lymphomonocytes; data were related to patients\x92 clinical, serological and histopathological characteristics. The presence of IL‐18 was determined in gland and saliva samples.
Results
P2X7R expression was significantly higher in salivary glands from individuals with pSS than in those from non‐SS and CTL subjects. Accordingly, the gene expression levels of the inflammasome components NLRP3, ASC and caspase‐1 were significantly higher in pSS gland specimens, and this was paralleled by an increased expression of mature IL‐18 in pSS saliva samples. The expression of both the P2X7R and the inflammasome components was a marker of disease‐related glandular involvement, being increased in patients with anti‐Ro/SSA positivity and correlated with focus score.
Conclusion
The results of this study suggest an involvement of the P2X7R–inflammasome–caspase‐1–IL‐18 axis in the development of pSS exocrinopathy. This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies. |
| doi_str_mv | 10.1111/joim.12115 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1443413146</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1443413146</sourcerecordid><originalsourceid>FETCH-LOGICAL-j2705-5dbdccd2831b08c77a1921614fc12870c1ffac1b4a6b23aee7d2e895ec0c3c03</originalsourceid><addsrcrecordid>eNo9kUtOw0AMhkcIREthwwHQ7GCTMp7Jc4kqHkVFRaILdtFk4rSJMpmQaQRlxR24CxfgJpyE9AHe2LI__7L8E3IKbAhdXBYm10PgAN4e6YPwPYcHkb9P-izyXMcPOeuRI2sLxkAwnx2SHhdRVwi_T95nC6SP_DmgDSqsl6b5-fjMq6yUWktrNFJldF3iG11ISyVtTIk0r6g2aVvKZV7N6XKx7mw3uv1Vp2RrU9kNVze5ll3vqfj-mjdYnVtqV1XadMrH5CCTpcWTXR6Q2c31bHTnTKa349HVxCl4wDzHS5NUqZSHAhIWqiCQEHHwwc0U8DBgCrJMKkhc6SdcSMQg5RhGHiqmhGJiQC62snVjXlq0y1jnVmFZygpNa2NwXeGCANfv0LMd2iYa03h3fPz3rg6ALfCal7j6nwOL10bEayPijRHx_XT8sKnELzOIfxo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1443413146</pqid></control><display><type>article</type><title>The P2X7 receptor–inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome</title><source>Wiley Free Content</source><source>MEDLINE</source><source>IngentaConnect Free/Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Baldini, C. ; Rossi, C. ; Ferro, F. ; Santini, E. ; Seccia, V. ; Donati, V. ; Solini, A.</creator><creatorcontrib>Baldini, C. ; Rossi, C. ; Ferro, F. ; Santini, E. ; Seccia, V. ; Donati, V. ; Solini, A.</creatorcontrib><description>Objective
Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7R)–NLRP3 inflammasome complex modulates the release of the inflammatory cytokines IL‐1β and IL‐18. The presence of P2X7R in salivary glands suggests an interesting scenario for the initiation and amplification of the innate immune response in pSS. Therefore, the aim of this study was to assess the role of the P2X7R–NLRP3 inflammasome in pSS.
Subjects and Methods
Twenty‐one consecutive patients with pSS according to the American–European Consensus Group criteria and 15 patients with sicca syndrome (i.e. without Sjögren's syndrome, non‐SS) were enrolled in this study, together with six control (CTL) subjects. Expression of the P2X7R‐NLRP3 platform and IL‐18 was determined by real‐time PCR and western blotting in gland specimens and peripheral lymphomonocytes; data were related to patients\x92 clinical, serological and histopathological characteristics. The presence of IL‐18 was determined in gland and saliva samples.
Results
P2X7R expression was significantly higher in salivary glands from individuals with pSS than in those from non‐SS and CTL subjects. Accordingly, the gene expression levels of the inflammasome components NLRP3, ASC and caspase‐1 were significantly higher in pSS gland specimens, and this was paralleled by an increased expression of mature IL‐18 in pSS saliva samples. The expression of both the P2X7R and the inflammasome components was a marker of disease‐related glandular involvement, being increased in patients with anti‐Ro/SSA positivity and correlated with focus score.
Conclusion
The results of this study suggest an involvement of the P2X7R–inflammasome–caspase‐1–IL‐18 axis in the development of pSS exocrinopathy. This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies.</description><identifier>ISSN: 0954-6820</identifier><identifier>EISSN: 1365-2796</identifier><identifier>DOI: 10.1111/joim.12115</identifier><identifier>PMID: 23906036</identifier><language>eng</language><publisher>England</publisher><subject>Blotting, Western ; Carrier Proteins - analysis ; Carrier Proteins - physiology ; Case-Control Studies ; Female ; Humans ; inflammasome ; Inflammasomes - physiology ; Inflammation - physiopathology ; Interleukin-18 - analysis ; Interleukin-18 - physiology ; Interleukin-1beta - analysis ; Interleukin-1beta - physiology ; interleukin‐18 ; Middle Aged ; Monocytes - chemistry ; Monocytes - physiology ; NLR Family, Pyrin Domain-Containing 3 Protein ; P2X7 receptor ; Real-Time Polymerase Chain Reaction ; Receptors, Purinergic P2X7 - analysis ; Receptors, Purinergic P2X7 - physiology ; Salivary Glands - chemistry ; Salvia - chemistry ; Sjogren's Syndrome - immunology ; Sjogren's Syndrome - physiopathology ; Sjögren's syndrome</subject><ispartof>Journal of internal medicine, 2013-11, Vol.274 (5), p.480-489</ispartof><rights>2013 The Association for the Publication of the Journal of Internal Medicine</rights><rights>2013 The Association for the Publication of the Journal of Internal Medicine.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjoim.12115$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjoim.12115$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23906036$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baldini, C.</creatorcontrib><creatorcontrib>Rossi, C.</creatorcontrib><creatorcontrib>Ferro, F.</creatorcontrib><creatorcontrib>Santini, E.</creatorcontrib><creatorcontrib>Seccia, V.</creatorcontrib><creatorcontrib>Donati, V.</creatorcontrib><creatorcontrib>Solini, A.</creatorcontrib><title>The P2X7 receptor–inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome</title><title>Journal of internal medicine</title><addtitle>J Intern Med</addtitle><description>Objective
Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7R)–NLRP3 inflammasome complex modulates the release of the inflammatory cytokines IL‐1β and IL‐18. The presence of P2X7R in salivary glands suggests an interesting scenario for the initiation and amplification of the innate immune response in pSS. Therefore, the aim of this study was to assess the role of the P2X7R–NLRP3 inflammasome in pSS.
Subjects and Methods
Twenty‐one consecutive patients with pSS according to the American–European Consensus Group criteria and 15 patients with sicca syndrome (i.e. without Sjögren's syndrome, non‐SS) were enrolled in this study, together with six control (CTL) subjects. Expression of the P2X7R‐NLRP3 platform and IL‐18 was determined by real‐time PCR and western blotting in gland specimens and peripheral lymphomonocytes; data were related to patients\x92 clinical, serological and histopathological characteristics. The presence of IL‐18 was determined in gland and saliva samples.
Results
P2X7R expression was significantly higher in salivary glands from individuals with pSS than in those from non‐SS and CTL subjects. Accordingly, the gene expression levels of the inflammasome components NLRP3, ASC and caspase‐1 were significantly higher in pSS gland specimens, and this was paralleled by an increased expression of mature IL‐18 in pSS saliva samples. The expression of both the P2X7R and the inflammasome components was a marker of disease‐related glandular involvement, being increased in patients with anti‐Ro/SSA positivity and correlated with focus score.
Conclusion
The results of this study suggest an involvement of the P2X7R–inflammasome–caspase‐1–IL‐18 axis in the development of pSS exocrinopathy. This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies.</description><subject>Blotting, Western</subject><subject>Carrier Proteins - analysis</subject><subject>Carrier Proteins - physiology</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Humans</subject><subject>inflammasome</subject><subject>Inflammasomes - physiology</subject><subject>Inflammation - physiopathology</subject><subject>Interleukin-18 - analysis</subject><subject>Interleukin-18 - physiology</subject><subject>Interleukin-1beta - analysis</subject><subject>Interleukin-1beta - physiology</subject><subject>interleukin‐18</subject><subject>Middle Aged</subject><subject>Monocytes - chemistry</subject><subject>Monocytes - physiology</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein</subject><subject>P2X7 receptor</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Purinergic P2X7 - analysis</subject><subject>Receptors, Purinergic P2X7 - physiology</subject><subject>Salivary Glands - chemistry</subject><subject>Salvia - chemistry</subject><subject>Sjogren's Syndrome - immunology</subject><subject>Sjogren's Syndrome - physiopathology</subject><subject>Sjögren's syndrome</subject><issn>0954-6820</issn><issn>1365-2796</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kUtOw0AMhkcIREthwwHQ7GCTMp7Jc4kqHkVFRaILdtFk4rSJMpmQaQRlxR24CxfgJpyE9AHe2LI__7L8E3IKbAhdXBYm10PgAN4e6YPwPYcHkb9P-izyXMcPOeuRI2sLxkAwnx2SHhdRVwi_T95nC6SP_DmgDSqsl6b5-fjMq6yUWktrNFJldF3iG11ISyVtTIk0r6g2aVvKZV7N6XKx7mw3uv1Vp2RrU9kNVze5ll3vqfj-mjdYnVtqV1XadMrH5CCTpcWTXR6Q2c31bHTnTKa349HVxCl4wDzHS5NUqZSHAhIWqiCQEHHwwc0U8DBgCrJMKkhc6SdcSMQg5RhGHiqmhGJiQC62snVjXlq0y1jnVmFZygpNa2NwXeGCANfv0LMd2iYa03h3fPz3rg6ALfCal7j6nwOL10bEayPijRHx_XT8sKnELzOIfxo</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Baldini, C.</creator><creator>Rossi, C.</creator><creator>Ferro, F.</creator><creator>Santini, E.</creator><creator>Seccia, V.</creator><creator>Donati, V.</creator><creator>Solini, A.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201311</creationdate><title>The P2X7 receptor–inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome</title><author>Baldini, C. ; Rossi, C. ; Ferro, F. ; Santini, E. ; Seccia, V. ; Donati, V. ; Solini, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j2705-5dbdccd2831b08c77a1921614fc12870c1ffac1b4a6b23aee7d2e895ec0c3c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Blotting, Western</topic><topic>Carrier Proteins - analysis</topic><topic>Carrier Proteins - physiology</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Humans</topic><topic>inflammasome</topic><topic>Inflammasomes - physiology</topic><topic>Inflammation - physiopathology</topic><topic>Interleukin-18 - analysis</topic><topic>Interleukin-18 - physiology</topic><topic>Interleukin-1beta - analysis</topic><topic>Interleukin-1beta - physiology</topic><topic>interleukin‐18</topic><topic>Middle Aged</topic><topic>Monocytes - chemistry</topic><topic>Monocytes - physiology</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein</topic><topic>P2X7 receptor</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Purinergic P2X7 - analysis</topic><topic>Receptors, Purinergic P2X7 - physiology</topic><topic>Salivary Glands - chemistry</topic><topic>Salvia - chemistry</topic><topic>Sjogren's Syndrome - immunology</topic><topic>Sjogren's Syndrome - physiopathology</topic><topic>Sjögren's syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baldini, C.</creatorcontrib><creatorcontrib>Rossi, C.</creatorcontrib><creatorcontrib>Ferro, F.</creatorcontrib><creatorcontrib>Santini, E.</creatorcontrib><creatorcontrib>Seccia, V.</creatorcontrib><creatorcontrib>Donati, V.</creatorcontrib><creatorcontrib>Solini, A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of internal medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baldini, C.</au><au>Rossi, C.</au><au>Ferro, F.</au><au>Santini, E.</au><au>Seccia, V.</au><au>Donati, V.</au><au>Solini, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The P2X7 receptor–inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome</atitle><jtitle>Journal of internal medicine</jtitle><addtitle>J Intern Med</addtitle><date>2013-11</date><risdate>2013</risdate><volume>274</volume><issue>5</issue><spage>480</spage><epage>489</epage><pages>480-489</pages><issn>0954-6820</issn><eissn>1365-2796</eissn><abstract>Objective
Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7R)–NLRP3 inflammasome complex modulates the release of the inflammatory cytokines IL‐1β and IL‐18. The presence of P2X7R in salivary glands suggests an interesting scenario for the initiation and amplification of the innate immune response in pSS. Therefore, the aim of this study was to assess the role of the P2X7R–NLRP3 inflammasome in pSS.
Subjects and Methods
Twenty‐one consecutive patients with pSS according to the American–European Consensus Group criteria and 15 patients with sicca syndrome (i.e. without Sjögren's syndrome, non‐SS) were enrolled in this study, together with six control (CTL) subjects. Expression of the P2X7R‐NLRP3 platform and IL‐18 was determined by real‐time PCR and western blotting in gland specimens and peripheral lymphomonocytes; data were related to patients\x92 clinical, serological and histopathological characteristics. The presence of IL‐18 was determined in gland and saliva samples.
Results
P2X7R expression was significantly higher in salivary glands from individuals with pSS than in those from non‐SS and CTL subjects. Accordingly, the gene expression levels of the inflammasome components NLRP3, ASC and caspase‐1 were significantly higher in pSS gland specimens, and this was paralleled by an increased expression of mature IL‐18 in pSS saliva samples. The expression of both the P2X7R and the inflammasome components was a marker of disease‐related glandular involvement, being increased in patients with anti‐Ro/SSA positivity and correlated with focus score.
Conclusion
The results of this study suggest an involvement of the P2X7R–inflammasome–caspase‐1–IL‐18 axis in the development of pSS exocrinopathy. This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies.</abstract><cop>England</cop><pmid>23906036</pmid><doi>10.1111/joim.12115</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Free Content; MEDLINE; IngentaConnect Free/Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Blotting, Western Carrier Proteins - analysis Carrier Proteins - physiology Case-Control Studies Female Humans inflammasome Inflammasomes - physiology Inflammation - physiopathology Interleukin-18 - analysis Interleukin-18 - physiology Interleukin-1beta - analysis Interleukin-1beta - physiology interleukin‐18 Middle Aged Monocytes - chemistry Monocytes - physiology NLR Family, Pyrin Domain-Containing 3 Protein P2X7 receptor Real-Time Polymerase Chain Reaction Receptors, Purinergic P2X7 - analysis Receptors, Purinergic P2X7 - physiology Salivary Glands - chemistry Salvia - chemistry Sjogren's Syndrome - immunology Sjogren's Syndrome - physiopathology Sjögren's syndrome |
| title | The P2X7 receptor–inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome |
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