Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients
•MIF and LPS induce the Th17 cytokine secretion profile in PBMC from RA patients.•In a Mexican-Mestizo population, the most frequent MIF haplotypes were 5G, 6G, and 7C.•MIF haplotypes modulate the secretion of cytokines related to the Th17 profile in PBMC cultures. Rheumatoid arthritis (RA) is a chr...
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| Veröffentlicht in: | Cytokine (Philadelphia, Pa.) Pa.), 2019-03, Vol.115, p.89-96 |
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| creator | Hernández-Palma, Luis Alexis García-Arellano, Samuel Bucala, Richard Llamas-Covarrubias, Mara Anaís De la Cruz-Mosso, Ulises Oregon-Romero, Edith Cerpa-Cruz, Sergio Parra-Rojas, Isela Plascencia-Hernández, Arturo Muñoz-Valle, José Francisco |
| description | •MIF and LPS induce the Th17 cytokine secretion profile in PBMC from RA patients.•In a Mexican-Mestizo population, the most frequent MIF haplotypes were 5G, 6G, and 7C.•MIF haplotypes modulate the secretion of cytokines related to the Th17 profile in PBMC cultures.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The −794 CATT5-8 and −173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients. |
| doi_str_mv | 10.1016/j.cyto.2018.11.014 |
| format | Article |
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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The −794 CATT5-8 and −173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.</description><identifier>ISSN: 1043-4666</identifier><identifier>EISSN: 1096-0023</identifier><identifier>DOI: 10.1016/j.cyto.2018.11.014</identifier><identifier>PMID: 30467094</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Arthritis, Rheumatoid - genetics ; Cytokines - genetics ; Female ; Haplotypes ; Haplotypes - genetics ; Humans ; Intramolecular Oxidoreductases - genetics ; Leukocytes, Mononuclear - metabolism ; Lipopolysaccharide ; Macrophage Migration-Inhibitory Factors - genetics ; Male ; Middle Aged ; MIF ; Polymorphism, Genetic - genetics ; Promoter Regions, Genetic - genetics ; Rheumatoid arthritis ; Th17 Cells - metabolism ; Th17 profile cytokines</subject><ispartof>Cytokine (Philadelphia, Pa.), 2019-03, Vol.115, p.89-96</ispartof><rights>2018 Elsevier Ltd</rights><rights>Copyright © 2018 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-77eb0875b101a67dd2e5fa50785f1fcefbc4d862c01100b367dfdd4cf9ee12ff3</citedby><cites>FETCH-LOGICAL-c356t-77eb0875b101a67dd2e5fa50785f1fcefbc4d862c01100b367dfdd4cf9ee12ff3</cites><orcidid>0000-0002-9213-8263</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cyto.2018.11.014$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30467094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hernández-Palma, Luis Alexis</creatorcontrib><creatorcontrib>García-Arellano, Samuel</creatorcontrib><creatorcontrib>Bucala, Richard</creatorcontrib><creatorcontrib>Llamas-Covarrubias, Mara Anaís</creatorcontrib><creatorcontrib>De la Cruz-Mosso, Ulises</creatorcontrib><creatorcontrib>Oregon-Romero, Edith</creatorcontrib><creatorcontrib>Cerpa-Cruz, Sergio</creatorcontrib><creatorcontrib>Parra-Rojas, Isela</creatorcontrib><creatorcontrib>Plascencia-Hernández, Arturo</creatorcontrib><creatorcontrib>Muñoz-Valle, José Francisco</creatorcontrib><title>Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients</title><title>Cytokine (Philadelphia, Pa.)</title><addtitle>Cytokine</addtitle><description>•MIF and LPS induce the Th17 cytokine secretion profile in PBMC from RA patients.•In a Mexican-Mestizo population, the most frequent MIF haplotypes were 5G, 6G, and 7C.•MIF haplotypes modulate the secretion of cytokines related to the Th17 profile in PBMC cultures.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The −794 CATT5-8 and −173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.</description><subject>Adult</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Cytokines - genetics</subject><subject>Female</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Humans</subject><subject>Intramolecular Oxidoreductases - genetics</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Lipopolysaccharide</subject><subject>Macrophage Migration-Inhibitory Factors - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>MIF</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Rheumatoid arthritis</subject><subject>Th17 Cells - metabolism</subject><subject>Th17 profile cytokines</subject><issn>1043-4666</issn><issn>1096-0023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFvFSEUhSdGY2vbP-DCsHQzIzAMvJe4MY1Pm7Tppq4JA5cMTwZGYIzvL_krZfKqS1fcxTnf5Z7TNG8J7ggm_MOx06cSO4rJriOkw4S9aC4J3vMWY9q_3GbWt4xzftG8yfmIMd73QrxuLnrMuMB7dtn8PqxBFxeD8ujh7oCWFOdYIKFJLT6W0wIZzdGsXhVATxMRbYJtNmjb_d0FQPBrSZBzZSAX0ALJLROkyht9jKa6Qwyr9qAS0uB9RrbuQDqGkqJHeR2PoEtGKhiUJlhnVaIzSKUyJVdcRosqDkLJ180rq3yGm-f3qvl2-Px0-7W9f_xyd_vpvtX9wEsrBIx4J4axZqS4MIbCYNWAxW6wxGqwo2Zmx6nGhGA89lVijWHa7gEItba_at6fuTWLHyvkImeXt5-rAHHNkpJeMEEoo1VKz1KdYs4JrFySm1U6SYLl1pE8yi0nuXUkCZG1o2p698xfxxnMP8vfUqrg41kA9cqfDpLMuiagwbhUo5Imuv_x_wA_4aj_</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Hernández-Palma, Luis Alexis</creator><creator>García-Arellano, Samuel</creator><creator>Bucala, Richard</creator><creator>Llamas-Covarrubias, Mara Anaís</creator><creator>De la Cruz-Mosso, Ulises</creator><creator>Oregon-Romero, Edith</creator><creator>Cerpa-Cruz, Sergio</creator><creator>Parra-Rojas, Isela</creator><creator>Plascencia-Hernández, Arturo</creator><creator>Muñoz-Valle, José Francisco</creator><general>Elsevier Ltd</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>7X8</scope><orcidid>https://orcid.org/0000-0002-9213-8263</orcidid></search><sort><creationdate>201903</creationdate><title>Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients</title><author>Hernández-Palma, Luis Alexis ; García-Arellano, Samuel ; Bucala, Richard ; Llamas-Covarrubias, Mara Anaís ; De la Cruz-Mosso, Ulises ; Oregon-Romero, Edith ; Cerpa-Cruz, Sergio ; Parra-Rojas, Isela ; Plascencia-Hernández, Arturo ; Muñoz-Valle, José Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-77eb0875b101a67dd2e5fa50785f1fcefbc4d862c01100b367dfdd4cf9ee12ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Arthritis, Rheumatoid - genetics</topic><topic>Cytokines - genetics</topic><topic>Female</topic><topic>Haplotypes</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>Intramolecular Oxidoreductases - genetics</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Lipopolysaccharide</topic><topic>Macrophage Migration-Inhibitory Factors - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>MIF</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Rheumatoid arthritis</topic><topic>Th17 Cells - metabolism</topic><topic>Th17 profile cytokines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hernández-Palma, Luis Alexis</creatorcontrib><creatorcontrib>García-Arellano, Samuel</creatorcontrib><creatorcontrib>Bucala, Richard</creatorcontrib><creatorcontrib>Llamas-Covarrubias, Mara Anaís</creatorcontrib><creatorcontrib>De la Cruz-Mosso, Ulises</creatorcontrib><creatorcontrib>Oregon-Romero, Edith</creatorcontrib><creatorcontrib>Cerpa-Cruz, Sergio</creatorcontrib><creatorcontrib>Parra-Rojas, Isela</creatorcontrib><creatorcontrib>Plascencia-Hernández, Arturo</creatorcontrib><creatorcontrib>Muñoz-Valle, José Francisco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cytokine (Philadelphia, Pa.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hernández-Palma, Luis Alexis</au><au>García-Arellano, Samuel</au><au>Bucala, Richard</au><au>Llamas-Covarrubias, Mara Anaís</au><au>De la Cruz-Mosso, Ulises</au><au>Oregon-Romero, Edith</au><au>Cerpa-Cruz, Sergio</au><au>Parra-Rojas, Isela</au><au>Plascencia-Hernández, Arturo</au><au>Muñoz-Valle, José Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients</atitle><jtitle>Cytokine (Philadelphia, Pa.)</jtitle><addtitle>Cytokine</addtitle><date>2019-03</date><risdate>2019</risdate><volume>115</volume><spage>89</spage><epage>96</epage><pages>89-96</pages><issn>1043-4666</issn><eissn>1096-0023</eissn><abstract>•MIF and LPS induce the Th17 cytokine secretion profile in PBMC from RA patients.•In a Mexican-Mestizo population, the most frequent MIF haplotypes were 5G, 6G, and 7C.•MIF haplotypes modulate the secretion of cytokines related to the Th17 profile in PBMC cultures.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The −794 CATT5-8 and −173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30467094</pmid><doi>10.1016/j.cyto.2018.11.014</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-9213-8263</orcidid></addata></record> |
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| subjects | Adult Arthritis, Rheumatoid - genetics Cytokines - genetics Female Haplotypes Haplotypes - genetics Humans Intramolecular Oxidoreductases - genetics Leukocytes, Mononuclear - metabolism Lipopolysaccharide Macrophage Migration-Inhibitory Factors - genetics Male Middle Aged MIF Polymorphism, Genetic - genetics Promoter Regions, Genetic - genetics Rheumatoid arthritis Th17 Cells - metabolism Th17 profile cytokines |
| title | Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients |
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