Rheumatoid arthritis synovial fibroblasts (RASFs) contribute to synovial inflammation and bone destruction by producing a pleiotropic cytokine interleukin-6 (IL-6). However, the molecular mechanisms through which IL-6 propels RASFs to contribute to bone loss are not fully understood. In the present study, we investigated the effect of IL-6 and IL-6 receptor (IL-6/IL-6R)-induced trans-signaling in human RASFs.
View Article and Find Full Text PDFObjective: Rheumatoid arthritis synovial fibroblasts (RASFs) are crucial mediators of synovial inflammation and joint destruction. However, their intrinsic immunoregulatory mechanisms under chronic inflammation remain unclear. Thus, the present study was undertaken to understand the role of a newly identified GTPase, guanylate binding protein 5 (GBP-5), in RA pathogenesis.
View Article and Find Full Text PDFHuman IFNs are secreted cytokines shown to stimulate the expression of over one thousand genes. These IFN-inducible genes primarily encode four major protein families, known as IFN-stimulated GTPases (ISGs), namely myxovirus-resistance proteins, guanylate-binding proteins (GBPs), p47 immunity-related GTPases and very large inducible guanosine triphosphate hydrolases (GTPases). These families respond specifically to type I or II IFNs and are well reported in coordinating immunity against some well known as well as newly discovered viral, bacterial and parasitic infections.
View Article and Find Full Text PDFMonosodium urate (MSU) crystals activate inflammatory pathways that overlap with interleukin-1β (IL-1β) signaling. However, the post-translational mechanisms involved and the role of signaling proteins in this activation are unknown. In the present study, we investigated the intracellular signaling mechanisms involved in MSU-induced activation of THP-1 macrophages and human nondiseased synovial fibroblasts (NLSFs) and the in vivo efficacy of an inhibitor of tumor growth factor-β (TGF-β)-activated kinase 1 (TAK1), 5Z-7-oxozeaenol, in MSU-induced paw inflammation in C57BL/6 mice.
View Article and Find Full Text PDFRheumatoid arthritis (RA) is characterized by hyperplastic pannus formation mediated by activated synovial fibroblasts (RASFs) that cause joint destruction. We have shown earlier that RASFs exhibit resistance to apoptosis, primarily as a result of enhanced expression of myeloid cell leukemia-1 (Mcl-1). In this study, we discovered that ursolic acid (UA), a plant-derived pentacyclic triterpenoid, selectively induces B-cell lymphoma 2 homology 3-only protein Noxa in human RASFs.
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