HLA-B27 alters the response to tumor necrosis factor α and promotes osteoclastogenesis in bone marrow monocytes from HLA-B27-transgenic rats.
HLA-B27 alters the response to tumor necrosis factor α and promotes osteoclastogenesis in bone marrow monocytes from HLA-B27-transgenic rats.
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DOI：
10.1002/art.38001
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发表时间：
2013-08
影响因子：
--
通讯作者：
Colbert, Robert A.
中科院分区：
文献类型：
--
作者：
Layh-Schmitt, Gerlinde;Yang, Eva Y.;Kwon, Grace;Colbert, Robert A.
To determine whether HLA-B27 expression alters the response of bone marrow monocytes (BMMo) from HLA-B27/human β2-microglobulin transgenic (B27-Tg) rats to tumor necrosis factor-α (TNFα), and whether this affects cells involved in bone homeostasis. BMMo were treated with receptor activator of NF-κB ligand or TNFα to promote osteoclast formation. Osteoclasts were quantified by counting. Gene expression was measured using quantitative polymerase chain reaction, and protein was detected by enzyme-linked immunosorbent assay, immunoblotting, or immunofluorescence. Effects of endogenously produced cytokines on osteoclast formation were determined with neutralizing antibodies. TNFα enhanced osteoclast formation 2.5-fold in HLA-B27-expressing cells compared to either wild type or HLA-B7/human β2-microglobulin expressing monocytes. TNFα induced approximately 4-fold upregulation of HLA-B27, which was associated with accumulation of misfolded heavy chains, binding of the ER chaperone BiP, and activation of an ER stress response, which was not seen with HLA-B7. No differences were seen with RANKL-induced osteoclastogenesis. Enhanced interleukin-1α (IL-1α) production from ER stressed B27-Tg BMMo was found to be necessary and sufficient for enhanced osteoclast formation. However, B27-Tg BMMo also produced more interferon-β (IFNβ), which attenuated the effect of IL-1α on osteoclast formation. HLA-B27-induced ER stress alters the response of BMMo from B27-Tg rats to TNFα, which is associated with enhanced production of IL-1α and IFNβ, cytokines that exhibit opposing effects on osteoclast formation. The altered response of cells expressing HLA-B27 to pro-inflammatory cytokines suggests that this MHC class I allele may contribute to the pathogenesis of spondyloarthritis and its unique phenotype through downstream effects involving alterations in bone homeostasis.
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影响因子：
16
作者：
Ganley IG;Wong PM;Gammoh N;Jiang X
通讯作者：
Jiang X
影响因子：
27.4
作者：
DONNELLY, S;DOYLE, DV;SPECTOR, TD
通讯作者：
SPECTOR, TD
影响因子：
--
作者：
Appel, Heiner;Kuhne, Maren;Loddenkemper, Christoph
通讯作者：
Loddenkemper, Christoph
影响因子：
4.9
作者：
Klingberg E;Lorentzon M;Mellström D;Geijer M;Göthlin J;Hilme E;Hedberg M;Carlsten H;Forsblad-d'Elia H
通讯作者：
Forsblad-d'Elia H
影响因子：
8.7
作者：
Colbert RA;DeLay ML;Klenk EI;Layh-Schmitt G
通讯作者：
Layh-Schmitt G