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Abundant expression of the IL-23 subunit p19, but low levels of bioactive IL-23 in the rheumatoid synovium


Brentano, F; Ospelt, C; Stanczyk, J; Gay, R E; Gay, S; Kyburz, D (2009). Abundant expression of the IL-23 subunit p19, but low levels of bioactive IL-23 in the rheumatoid synovium. Annals of the Rheumatic Diseases, 68(1):143-150.

Abstract

OBJECTIVE: IL-23, composed of a p19 and a p40 subunit, is suggested to play key roles in rheumatoid arthritis (RA), dependent on the promotion and proliferation of IL-17-producing Th17 T-cells. However, previous studies on IL-23 expression in human tissues were based on p19 only. We aimed to study the expression and regulation of both IL-23 subunits, p19 and p40, in RA compared to osteoarthritis (OA) patients. METHODS: The expression of p19 and p40 in synovial tissues was analyzed by in-situ hybridization and immunohistochemistry. IL-23 in RA and OA synovial fluids and sera was determined by ELISA. TLR-dependent induction of p19, p40 and bioactive IL-23 was determined in RASF, monocytes and MDDC by RT-PCR, Real-time PCR, Western-blot and functional-assays. RESULTS: The p19 subunit was abundantly expressed in RA but not in OA synovial tissues. p19 was most prominently expressed by RASF in the synovial lining layer and at the site of invasion, but no heterodimeric IL-23 was detected at these sites. Correspondingly, soluble IL-23 was not detectable or found at very low levels in synovial fluids and sera of patients with RA. By in-vitro experiments, we confirmed that TLR-activated RASF expressed p19 but not p40, in contrast to monocytes, which produced IL-23 following TLR stimulation. CONCLUSION: The TLR-dependent induction of p19 but not p40 in RASF and the abundant expression of p19 along with the low or undetectable levels of IL-23 in RA patients, gives strong evidence that p19 does not necessarily indicate the presence of IL-23 as it has been proposed so far.

OBJECTIVE: IL-23, composed of a p19 and a p40 subunit, is suggested to play key roles in rheumatoid arthritis (RA), dependent on the promotion and proliferation of IL-17-producing Th17 T-cells. However, previous studies on IL-23 expression in human tissues were based on p19 only. We aimed to study the expression and regulation of both IL-23 subunits, p19 and p40, in RA compared to osteoarthritis (OA) patients. METHODS: The expression of p19 and p40 in synovial tissues was analyzed by in-situ hybridization and immunohistochemistry. IL-23 in RA and OA synovial fluids and sera was determined by ELISA. TLR-dependent induction of p19, p40 and bioactive IL-23 was determined in RASF, monocytes and MDDC by RT-PCR, Real-time PCR, Western-blot and functional-assays. RESULTS: The p19 subunit was abundantly expressed in RA but not in OA synovial tissues. p19 was most prominently expressed by RASF in the synovial lining layer and at the site of invasion, but no heterodimeric IL-23 was detected at these sites. Correspondingly, soluble IL-23 was not detectable or found at very low levels in synovial fluids and sera of patients with RA. By in-vitro experiments, we confirmed that TLR-activated RASF expressed p19 but not p40, in contrast to monocytes, which produced IL-23 following TLR stimulation. CONCLUSION: The TLR-dependent induction of p19 but not p40 in RASF and the abundant expression of p19 along with the low or undetectable levels of IL-23 in RA patients, gives strong evidence that p19 does not necessarily indicate the presence of IL-23 as it has been proposed so far.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:05 Aug 2008 06:49
Last Modified:05 Apr 2016 12:25
Publisher:BMJ Publishing Group
ISSN:0003-4967
Publisher DOI:10.1136/ard.2007.082081
PubMed ID:18276743
Permanent URL: http://doi.org/10.5167/uzh-2879

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