Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis
Background. Cell signaling via Toll-like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent-onset RA, oste...
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| Format: | Article |
| Language: | English |
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Wiley
2008-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2008/132732 |
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| author | M. L. Kowalski A. Wolska J. Grzegorczyk J. Hilt M. Jarzebska M. Drobniewski M. Synder M. Kurowski |
| author_facet | M. L. Kowalski A. Wolska J. Grzegorczyk J. Hilt M. Jarzebska M. Drobniewski M. Synder M. Kurowski |
| author_sort | M. L. Kowalski |
| collection | DOAJ |
| description | Background. Cell signaling via Toll-like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent-onset RA, osteoarthrosis (OA), and healthy control (HC). Methods. PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll-like receptors mRNA in leukocytes was analyzed using real-time qPCR. Results. PBMCs from RA patients spontaneously produced less IL-6 and TNFα than cells from OA and HC subjects. LPS increased cytokines' production in all groups. In RA patients increase was dramatic (30 to 48-fold and 17 to 31-fold, for respective cytokines) compared to moderate (2 to 8-fold) in other groups. LPS induced 15-HETE generation in PBMCs from RA (mean 251%) and OA patients (mean 43%), although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients. Conclusion. PBMCs from recent-onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide. TLR expression is differentially regulated in healthy and arthritic subjects. |
| format | Article |
| id | doaj-art-2ad2337a0d074a3aa099b4758bf910f2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2ad2337a0d074a3aa099b4758bf910f22025-08-20T03:54:43ZengWileyMediators of Inflammation0962-93511466-18612008-01-01200810.1155/2008/132732132732Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid ArthritisM. L. Kowalski0A. Wolska1J. Grzegorczyk2J. Hilt3M. Jarzebska4M. Drobniewski5M. Synder6M. Kurowski7Department of Immunology, Rheumatology and Allergy, Chair of Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, PolandDepartment of Immunology, Rheumatology and Allergy, Chair of Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, PolandDepartment of Laboratory Medical Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, PolandDepartment of Immunology, Rheumatology and Allergy, Chair of Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, PolandDepartment of Immunology, Rheumatology and Allergy, Chair of Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, PolandDepartment of Orthopedics and Pediatric Orthopedics, Medical University of Lodz, Drewnowska 75, 91-002 Lodz, PolandDepartment of Orthopedics and Pediatric Orthopedics, Medical University of Lodz, Drewnowska 75, 91-002 Lodz, PolandDepartment of Immunology, Rheumatology and Allergy, Chair of Immunology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, PolandBackground. Cell signaling via Toll-like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent-onset RA, osteoarthrosis (OA), and healthy control (HC). Methods. PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll-like receptors mRNA in leukocytes was analyzed using real-time qPCR. Results. PBMCs from RA patients spontaneously produced less IL-6 and TNFα than cells from OA and HC subjects. LPS increased cytokines' production in all groups. In RA patients increase was dramatic (30 to 48-fold and 17 to 31-fold, for respective cytokines) compared to moderate (2 to 8-fold) in other groups. LPS induced 15-HETE generation in PBMCs from RA (mean 251%) and OA patients (mean 43%), although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients. Conclusion. PBMCs from recent-onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide. TLR expression is differentially regulated in healthy and arthritic subjects.http://dx.doi.org/10.1155/2008/132732 |
| spellingShingle | M. L. Kowalski A. Wolska J. Grzegorczyk J. Hilt M. Jarzebska M. Drobniewski M. Synder M. Kurowski Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis Mediators of Inflammation |
| title | Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis |
| title_full | Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis |
| title_fullStr | Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis |
| title_full_unstemmed | Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis |
| title_short | Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritis |
| title_sort | increased responsiveness to toll like receptor 4 stimulation in peripheral blood mononuclear cells from patients with recent onset rheumatoid arthritis |
| url | http://dx.doi.org/10.1155/2008/132732 |
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