Interleukin-10 inhibition of the progression of established collagen-induced arthritis
ABSTRACT Interleukin-10 (IL-10) is a potent inhibitor of the proinflammatory cytokines, including tumor necrosis factor alpha and IL-1, which are considered important in the pathogenesis of rheumatoid arthritis (RA). The study was undertaken to establish whether IL-10 can ameliorate arthritis in the collagen-induced arthritis (CIA) model of RA.
DBA/1 mice were immunized with bovine type II collagen in adjuvant, and treated daily after disease onset with recombinant murine IL-10 or with saline as a control. Mice were monitored for paw swelling and clinical score. Histologic analysis was also performed.
IL-10 treatment of established CIA inhibited paw swelling (P < 0.0001), as well as disease progression as defined by clinical score (P < 0.0002). Cartilage destruction, as assessed histologically, was reduced in IL-10-treated mice compared with controls (P < 0.01).
IL-10 suppresses established CIA, probably by inhibiting proinflammatory cytokine production. Our results, taken together with previously reported findings, indicate a potential therapeutic role for IL-10 in RA.
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ABSTRACT: Bone destruction at inflamed joints is an important complication associated with rheumatoid arthritis (RA). Interleukin-10 (IL-10) may suppress not only inflammation but also induction of osteoclasts that play key roles in the bone destruction. If IL-10-producing osteoblast-like cells are induced from patient somatic cells and transplanted back into the destructive bone lesion, such therapy may promote bone remodeling by the cooperative effects of IL-10 and osteoblasts. We transduced mouse fibroblasts with genes for IL-10 and Runx2 that is a crucial transcription factor for osteoblast differentiation. The IL-10-producing induced osteoblast-like cells (IL-10-iOBs) strongly expressed osteoblast-specific genes and massively produced bone matrix that were mineralized by calcium phosphate in vitro and in vivo. Culture supernatant of IL-10-iOBs significantly suppressed induction of osteoclast from RANKL-stimulated Raw264.7 cells as well as LPS-induced production of inflammatory cytokine by macrophages. The IL-10-iOBs may be applicable to novel cell-based therapy against bone destruction associated with RA. Copyright © 2014. Published by Elsevier Inc.Biochemical and Biophysical Research Communications 12/2014; 456(3). DOI:10.1016/j.bbrc.2014.12.040 · 2.28 Impact Factor
Dataset: KRG ginseng saponin MI-201401
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ABSTRACT: Although probiotics could confer health benefits to host physiology, their efficacy is strain specific. To identify anti-inflammatory probiotics, an ex vivo screening system was developed, and validated effector functions of selected candidates using experimental rheumatoid arthritis as an in vivo model. Lactobacillus helveticus HY7801 was selected as the best candidate. Oral administration of L. helveticus HY7801 prevented the development of collagen-induced experimental arthritis, and diminished disease progression and severity by reducing antigen specific IgG levels and inflammatory immune response. Administration of L. helveticus HY7801 may induce regulatory CD11c+ dendritic cells, which in turn induce a phenotypic alteration of immune cells by reducing pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-17A) while enhancing anti-inflammatory cytokine (IL-10) by CD4+ T cells. This study suggests that screening of probiotic strains based on the IL-10highIL-12low selection criterion may be applicable to identify anti-inflammatory probiotics as an efficacious food for treating inflammatory immune responses including rheumatoid arthritis.Journal of Functional Foods 03/2015; 13. DOI:10.1016/j.jff.2015.01.002 · 4.48 Impact Factor