-
Je něco špatně v tomto záznamu ?
Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis
M. Filková, Z. Vernerová, H. Hulejová, K. Prajzlerová, D. Veigl, K. Pavelka, J. Vencovský, L. Šenolt,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NT12440
MZ0
CEP - Centrální evidence projektů
- MeSH
- fibroblasty účinky léků metabolismus MeSH
- interleukiny metabolismus MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- myši MeSH
- podjednotky proteinů metabolismus MeSH
- psoriatická artritida metabolismus patologie MeSH
- revmatoidní artritida metabolismus patologie MeSH
- synoviální membrána patologie MeSH
- TNF-alfa farmakologie MeSH
- upregulace účinky léků genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Interleukin-35 (IL-35) is a heterodimeric member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. Expressed in murine Treg cells, IL-35 controls inflammatory diseases in mouse models. However, human IL-35 is expressed in Teff cells rather than in Treg cells and is shown to be upregulated under inflammatory conditions. Our aim was to examine the involvement of IL-35 in the pathogenesis of rheumatoid arthritis (RA). METHODS: Immunohistochemical and immunofluorescence analysis was used to determine the expression and localization of IL-35 and its subunits (p35/EBI3) and IL-35 receptor (IL12Rβ2/gp130) in RA, osteoarthritis (OA) and psoriatic arthritis (PsA) synovial tissues. Expression of p35/EBI3 subunits and release of inflammatory cytokines upon stimulation with IL-35 were assessed in RA synovial fibroblasts (SFs) and peripheral blood mononuclear cells (PBMCs). RESULTS: Both IL-35 and its subunits were upregulated in RA in comparison with OA or PsA synovium. Using cell-specific markers, p35 and EBI3 were identified in macrophages, dendritic cells, SFs, and T as well as B cells in RA synovium. Both p35 and EBI3 were induced by TNFα in RASFs and PBMCs. IL-35 dose-dependently upregulated release of pro-inflammatory mediators IL-1β, IL-6 and MCP-1 in PBMCs. While gp130 receptor subunit was upregulated in RA synovium and was expressed in RASFs and PBMCs, there was no difference in IL12Rβ2 expression subunit among tissues and its presence in RASFs was lacking. CONCLUSION: Upregulation of IL-35 at sites of inflammation in RA and its pro-inflammatory potential suggests that IL-35 might play an important role in RA pathogenesis.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc16000272
- 003
- CZ-PrNML
- 005
- 20170428100637.0
- 007
- ta
- 008
- 160108s2015 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.cyto.2015.01.019 $2 doi
- 035 __
- $a (PubMed)25697137
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Filková, Mária $u Institute of Rheumatology, Prague, Czech Republic. Electronic address: MariaFilkova@seznam.cz. $7 xx0074560
- 245 10
- $a Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis / $c M. Filková, Z. Vernerová, H. Hulejová, K. Prajzlerová, D. Veigl, K. Pavelka, J. Vencovský, L. Šenolt,
- 520 9_
- $a OBJECTIVE: Interleukin-35 (IL-35) is a heterodimeric member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. Expressed in murine Treg cells, IL-35 controls inflammatory diseases in mouse models. However, human IL-35 is expressed in Teff cells rather than in Treg cells and is shown to be upregulated under inflammatory conditions. Our aim was to examine the involvement of IL-35 in the pathogenesis of rheumatoid arthritis (RA). METHODS: Immunohistochemical and immunofluorescence analysis was used to determine the expression and localization of IL-35 and its subunits (p35/EBI3) and IL-35 receptor (IL12Rβ2/gp130) in RA, osteoarthritis (OA) and psoriatic arthritis (PsA) synovial tissues. Expression of p35/EBI3 subunits and release of inflammatory cytokines upon stimulation with IL-35 were assessed in RA synovial fibroblasts (SFs) and peripheral blood mononuclear cells (PBMCs). RESULTS: Both IL-35 and its subunits were upregulated in RA in comparison with OA or PsA synovium. Using cell-specific markers, p35 and EBI3 were identified in macrophages, dendritic cells, SFs, and T as well as B cells in RA synovium. Both p35 and EBI3 were induced by TNFα in RASFs and PBMCs. IL-35 dose-dependently upregulated release of pro-inflammatory mediators IL-1β, IL-6 and MCP-1 in PBMCs. While gp130 receptor subunit was upregulated in RA synovium and was expressed in RASFs and PBMCs, there was no difference in IL12Rβ2 expression subunit among tissues and its presence in RASFs was lacking. CONCLUSION: Upregulation of IL-35 at sites of inflammation in RA and its pro-inflammatory potential suggests that IL-35 might play an important role in RA pathogenesis.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a psoriatická artritida $x metabolismus $x patologie $7 D015535
- 650 _2
- $a revmatoidní artritida $x metabolismus $x patologie $7 D001172
- 650 _2
- $a fibroblasty $x účinky léků $x metabolismus $7 D005347
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mediátory zánětu $x metabolismus $7 D018836
- 650 _2
- $a interleukiny $x metabolismus $7 D007378
- 650 _2
- $a leukocyty mononukleární $x účinky léků $x metabolismus $7 D007963
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a podjednotky proteinů $x metabolismus $7 D021122
- 650 _2
- $a synoviální membrána $x patologie $7 D013583
- 650 _2
- $a TNF-alfa $x farmakologie $7 D014409
- 650 _2
- $a upregulace $x účinky léků $x genetika $7 D015854
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Vernerová, Zdenka, $u Institute of Pathology of the 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. $d 1960-2020 $7 jo2002104672
- 700 1_
- $a Hulejová, Hana $u Institute of Rheumatology, Prague, Czech Republic. $7 xx0077461
- 700 1_
- $a Prajzlerová, Klára $u Institute of Rheumatology, Prague, Czech Republic. $7 xx0210373
- 700 1_
- $a Veigl, David $u 1st Orthopedic Clinic, 1st Faculty of Medicine and Faculty Hospital Motol, Charles University in Prague, Prague, Czech Republic. $7 xx0143524
- 700 1_
- $a Pavelka, Karel, $u Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, 1st Faculty of Medicine, Charles University in Prague, Czech Republic. $d 1954- $7 jn99240000847
- 700 1_
- $a Vencovský, Jiří, $u Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, 1st Faculty of Medicine, Charles University in Prague, Czech Republic. $d 1953- $7 jo20000080529
- 700 1_
- $a Šenolt, Ladislav, $u Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, 1st Faculty of Medicine, Charles University in Prague, Czech Republic. $d 1976- $7 xx0056558
- 773 0_
- $w MED00001313 $t Cytokine $x 1096-0023 $g Roč. 73, č. 1 (2015), s. 36-43
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/25697137 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20160108 $b ABA008
- 991 __
- $a 20170428100958 $b ABA008
- 999 __
- $a ok $b bmc $g 1102553 $s 924478
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2015 $b 73 $c 1 $d 36-43 $e 20150216 $i 1096-0023 $m Cytokine (Philadelphia, Pa. Print) $n Cytokine $x MED00001313
- GRA __
- $a NT12440 $p MZ0
- LZP __
- $a Pubmed-20160108
