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Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis
OBJECTIVES: This study aims to investigate lymphoproliferation, cytokine production, and intracellular signaling molecules in peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and rheumatoid arthritis (RA) patients to understand the extent of the involvement of these pathw...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Turkish League Against Rheumatism
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945702/ https://www.ncbi.nlm.nih.gov/pubmed/33758811 http://dx.doi.org/10.46497/ArchRheumatol.2020.7481 |
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author | PRATAP, Uday P. HIMA, Lalgi KANNAN, Thangamani THYAGARAJAN, Chadrasekaran PRIYANKA, Hannah P. VASANTHAREKHA, Ramasamy PUSHPARANI, Anand THYAGARAJAN, Srinivasan |
author_facet | PRATAP, Uday P. HIMA, Lalgi KANNAN, Thangamani THYAGARAJAN, Chadrasekaran PRIYANKA, Hannah P. VASANTHAREKHA, Ramasamy PUSHPARANI, Anand THYAGARAJAN, Srinivasan |
author_sort | PRATAP, Uday P. |
collection | PubMed |
description | OBJECTIVES: This study aims to investigate lymphoproliferation, cytokine production, and intracellular signaling molecules in peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and rheumatoid arthritis (RA) patients to understand the extent of the involvement of these pathways in the pathogenesis of RA. PATIENTS AND METHODS: The study included 65 participants (29 males, 36 females; mean age 51.8±10.3 years; range, 37 to 71 years) who were categorized into four groups as healthy males (n=22, mean age 49.8±10.6 years; range, 39 to 65 years), male RA patients (n=7, mean age 51.8±13.9 years; range, 37 to 68 years), healthy females (n=20, mean age 53.7±8.8 years; range, 42 to 67 years), and female RA patients (n=16, mean age 52.9±10.4 years; range, 40 to 71 years). PBMCs were collected from the participants and analyzed for Concanavalin A (Con A)-induced lymphoproliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cytokine production, and phospho-signal transducer and activator of transcription 3 (p-STAT-3), phospho-extracellular-signal-regulated kinase (p-ERK), phospho-cAMP response element binding (p-CREB), and phospho-protein kinase B expressions using enzyme-linked immunosorbent assay. Short form of the Arthritis Impact Measurement Scales 2 and multidimensional health assessment questionnaire were used to measure the level of disability and the quality of life. RESULTS: In RA patients, production of Con A-induced interleukin (IL)-2 and IL-17 was higher in both sexes while interferon-gamma levels decreased in RA females alone. Expression of p-STAT-3 in PBMCs increased in RA males while it was unaltered in RA females. p-ERK expression was not altered while p-CREB expression was enhanced in RA males and females. Protein-protein interaction analyses demonstrated that these and other key signaling molecules were dysregulated in RA patients. CONCLUSION: Our results suggest that sex-based differences in RA pathogenesis result from differential alterations in signaling pathways to influence the inflammatory process. |
format | Online Article Text |
id | pubmed-7945702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Turkish League Against Rheumatism |
record_format | MEDLINE/PubMed |
spelling | pubmed-79457022021-03-22 Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis PRATAP, Uday P. HIMA, Lalgi KANNAN, Thangamani THYAGARAJAN, Chadrasekaran PRIYANKA, Hannah P. VASANTHAREKHA, Ramasamy PUSHPARANI, Anand THYAGARAJAN, Srinivasan Arch Rheumatol Original Article OBJECTIVES: This study aims to investigate lymphoproliferation, cytokine production, and intracellular signaling molecules in peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and rheumatoid arthritis (RA) patients to understand the extent of the involvement of these pathways in the pathogenesis of RA. PATIENTS AND METHODS: The study included 65 participants (29 males, 36 females; mean age 51.8±10.3 years; range, 37 to 71 years) who were categorized into four groups as healthy males (n=22, mean age 49.8±10.6 years; range, 39 to 65 years), male RA patients (n=7, mean age 51.8±13.9 years; range, 37 to 68 years), healthy females (n=20, mean age 53.7±8.8 years; range, 42 to 67 years), and female RA patients (n=16, mean age 52.9±10.4 years; range, 40 to 71 years). PBMCs were collected from the participants and analyzed for Concanavalin A (Con A)-induced lymphoproliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cytokine production, and phospho-signal transducer and activator of transcription 3 (p-STAT-3), phospho-extracellular-signal-regulated kinase (p-ERK), phospho-cAMP response element binding (p-CREB), and phospho-protein kinase B expressions using enzyme-linked immunosorbent assay. Short form of the Arthritis Impact Measurement Scales 2 and multidimensional health assessment questionnaire were used to measure the level of disability and the quality of life. RESULTS: In RA patients, production of Con A-induced interleukin (IL)-2 and IL-17 was higher in both sexes while interferon-gamma levels decreased in RA females alone. Expression of p-STAT-3 in PBMCs increased in RA males while it was unaltered in RA females. p-ERK expression was not altered while p-CREB expression was enhanced in RA males and females. Protein-protein interaction analyses demonstrated that these and other key signaling molecules were dysregulated in RA patients. CONCLUSION: Our results suggest that sex-based differences in RA pathogenesis result from differential alterations in signaling pathways to influence the inflammatory process. Turkish League Against Rheumatism 2020-04-27 /pmc/articles/PMC7945702/ /pubmed/33758811 http://dx.doi.org/10.46497/ArchRheumatol.2020.7481 Text en Copyright © 2020, Turkish League Against Rheumatism http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Article PRATAP, Uday P. HIMA, Lalgi KANNAN, Thangamani THYAGARAJAN, Chadrasekaran PRIYANKA, Hannah P. VASANTHAREKHA, Ramasamy PUSHPARANI, Anand THYAGARAJAN, Srinivasan Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis |
title | Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis |
title_full | Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis |
title_fullStr | Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis |
title_full_unstemmed | Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis |
title_short | Sex-Based Differences in the Cytokine Production and Intracellular Signaling Pathways in Patients With Rheumatoid Arthritis |
title_sort | sex-based differences in the cytokine production and intracellular signaling pathways in patients with rheumatoid arthritis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945702/ https://www.ncbi.nlm.nih.gov/pubmed/33758811 http://dx.doi.org/10.46497/ArchRheumatol.2020.7481 |
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