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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...

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Autores principales: PRATAP, Uday P., HIMA, Lalgi, KANNAN, Thangamani, THYAGARAJAN, Chadrasekaran, PRIYANKA, Hannah P., VASANTHAREKHA, Ramasamy, PUSHPARANI, Anand, THYAGARAJAN, Srinivasan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Turkish League Against Rheumatism 2020
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.
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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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