Abstract
To delineate the functional significance of IL-17 Receptor (IL-17RA) and characterize the IL-17 producing T cell (T h17) subpopulation in psoriatic arthritis (PsA). Mononuclear cells from blood and synovial fluid (SF) were obtained from PsA (n = 20), rheumatoid arthritis (RA, n = 20) and osteoarthritis (OA, n = 20) patients. Synoviocytes (FLS) were isolated from the synovium of RA (n = 5), PsA (n = 5) and OA (n = 5) patients. IL-17RA expression in FLS was identified by western blotting (WB) and flowcytometry. T lymphocytes derived from the SF of these patients were studied to identify and phenotype the T h17 cells. The functional significance of IL-17RA was determined by evaluating its regulatory role on the production of proinflammatory cytokines and endopeptidase. IL-17RA expression was found to be significantly higher in FLS of RA (15.7% ± 4.9) and PsA (4.5% ± 0.9) in comparison to OA (1.14% ± 0.9). Western blot analyses showed that the relative intensity (RI) of IL-17RA protein was higher in RA and PsA compared to OA (Fisher exact, P < 0.01). A significant enrichment of IL-17-producing CD4+ T cells (7.9% ± 2.8) was observed in the SF of PsA patients compared to that of OA patients (P < .001). Compared to OA-FLS, recombinant IL-17 induced higher levels of IL-6, IL-8, and MMP-3 production in PsA-FLS. Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3. This is the first report to demonstrate the functional significance of IL-17RA in PsA. Results of this study support the hypothesis that IL-17RA blocking antibodies have the potential to be a therapeutic option for psoriatic arthritis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 419-429 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Biochemistry |
| Volume | 359 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Jan 2012 |
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Keywords
- IL-17/IL-17R
- Psoriasis
- Psoriatic arthritis
- Synovial tissue
- Synoviocytes/FLS
- T 17 cells
ASJC Scopus subject areas
- Clinical Biochemistry
- Molecular Biology
- Cell Biology
Cite this
IL-17 receptor and its functional significance in psoriatic arthritis. / Raychaudhuri, Siba P; Raychaudhuri, Smriti K.; Genovese, Mark C.
In: Molecular and Cellular Biochemistry, Vol. 359, No. 1-2, 01.2012, p. 419-429.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IL-17 receptor and its functional significance in psoriatic arthritis
AU - Raychaudhuri, Siba P
AU - Raychaudhuri, Smriti K.
AU - Genovese, Mark C.
PY - 2012/1
Y1 - 2012/1
N2 - To delineate the functional significance of IL-17 Receptor (IL-17RA) and characterize the IL-17 producing T cell (T h17) subpopulation in psoriatic arthritis (PsA). Mononuclear cells from blood and synovial fluid (SF) were obtained from PsA (n = 20), rheumatoid arthritis (RA, n = 20) and osteoarthritis (OA, n = 20) patients. Synoviocytes (FLS) were isolated from the synovium of RA (n = 5), PsA (n = 5) and OA (n = 5) patients. IL-17RA expression in FLS was identified by western blotting (WB) and flowcytometry. T lymphocytes derived from the SF of these patients were studied to identify and phenotype the T h17 cells. The functional significance of IL-17RA was determined by evaluating its regulatory role on the production of proinflammatory cytokines and endopeptidase. IL-17RA expression was found to be significantly higher in FLS of RA (15.7% ± 4.9) and PsA (4.5% ± 0.9) in comparison to OA (1.14% ± 0.9). Western blot analyses showed that the relative intensity (RI) of IL-17RA protein was higher in RA and PsA compared to OA (Fisher exact, P < 0.01). A significant enrichment of IL-17-producing CD4+ T cells (7.9% ± 2.8) was observed in the SF of PsA patients compared to that of OA patients (P < .001). Compared to OA-FLS, recombinant IL-17 induced higher levels of IL-6, IL-8, and MMP-3 production in PsA-FLS. Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3. This is the first report to demonstrate the functional significance of IL-17RA in PsA. Results of this study support the hypothesis that IL-17RA blocking antibodies have the potential to be a therapeutic option for psoriatic arthritis.
AB - To delineate the functional significance of IL-17 Receptor (IL-17RA) and characterize the IL-17 producing T cell (T h17) subpopulation in psoriatic arthritis (PsA). Mononuclear cells from blood and synovial fluid (SF) were obtained from PsA (n = 20), rheumatoid arthritis (RA, n = 20) and osteoarthritis (OA, n = 20) patients. Synoviocytes (FLS) were isolated from the synovium of RA (n = 5), PsA (n = 5) and OA (n = 5) patients. IL-17RA expression in FLS was identified by western blotting (WB) and flowcytometry. T lymphocytes derived from the SF of these patients were studied to identify and phenotype the T h17 cells. The functional significance of IL-17RA was determined by evaluating its regulatory role on the production of proinflammatory cytokines and endopeptidase. IL-17RA expression was found to be significantly higher in FLS of RA (15.7% ± 4.9) and PsA (4.5% ± 0.9) in comparison to OA (1.14% ± 0.9). Western blot analyses showed that the relative intensity (RI) of IL-17RA protein was higher in RA and PsA compared to OA (Fisher exact, P < 0.01). A significant enrichment of IL-17-producing CD4+ T cells (7.9% ± 2.8) was observed in the SF of PsA patients compared to that of OA patients (P < .001). Compared to OA-FLS, recombinant IL-17 induced higher levels of IL-6, IL-8, and MMP-3 production in PsA-FLS. Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3. This is the first report to demonstrate the functional significance of IL-17RA in PsA. Results of this study support the hypothesis that IL-17RA blocking antibodies have the potential to be a therapeutic option for psoriatic arthritis.
KW - IL-17/IL-17R
KW - Psoriasis
KW - Psoriatic arthritis
KW - Synovial tissue
KW - Synoviocytes/FLS
KW - T 17 cells
UR - http://www.scopus.com/inward/record.url?scp=83555174764&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=83555174764&partnerID=8YFLogxK
U2 - 10.1007/s11010-011-1036-6
DO - 10.1007/s11010-011-1036-6
M3 - Article
VL - 359
SP - 419
EP - 429
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
SN - 0300-8177
IS - 1-2
ER -