http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Retinoic acid attenuates rheumatoid inflammation in mice.
Kwok, Seung-Ki,Park, Mi-Kyung,Cho, Mi-La,Oh, Hye-Jwa,Park, Eun-Mi,Lee, Dong-Gun,Lee, Jennifer,Kim, Ho-Youn,Park, Sung-Hwan American Association of Immunologists 2012 Journal of Immunology Vol. No.
<P>Retinoic acid is the active vitamin A derivative and is well-known to have diverse immunomodulatory actions. In this study, we investigated the impact of all-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, on the development of arthritis and the pathophysiologic mechanisms by which ATRA might have antiarthritic effects in animal model of rheumatoid arthritis (RA; collagen-induced arthritis [CIA] in DBA/1J mice). We showed that treatment with ATRA markedly suppressed the clinical and histologic signs of arthritis in the CIA mice. It reduced the expression of IL-17 in the arthritic joints. Interestingly, Foxp3(+) regulatory T cells were markedly increased and IL-17-producing CD4(+) T cells (Th17 cells) were decreased in the spleens of ATRA-treated mice. In vitro treatment with ATRA induced the expression of Foxp3 and repressed the IL-17 expression in the CD4(+) T cells in mice. ATRA suppressed the production of total IgG and IgG2a in splenocytes that were stimulated by LPS. It also reduced serum levels of total IgG and IgG2 anti-collagen Abs and germinal center formation in CIA mice. In addition, the ATRA-treated mice showed decreased osteoclast formation in arthritic joints. Moreover, ATRA downregulated the expression of receptor activator of NF-관B ligand, the leading player of osteoclastogenesis, in the CD4(+) T cells and fibroblast-like synoviocytes from patients with RA. Furthermore, ATRA prevented both human monocytes and mice bone marrow-derived monocytes/macrophage cells from differentiating into osteoclasts. These data suggest ATRA might be an effective treatment modality for RA patients.</P>
Lee, Seon-Yeong,Moon, Su-Jin,Kim, Eun-Kyung,Seo, Hyeon-Beom,Yang, Eun-Ji,Son, Hye-Jin,Kim, Jae-Kyung,Min, Jun-Ki,Park, Sung-Hwan,Cho, Mi-La American Association of Immunologists 2017 Journal of Immunology Vol. No.
<P>Circulating autoantibodies and immune complex deposition are pathological hallmarks of systemic lupus erythematosus (SLE). B cell differentiation into plasma cells (PCs) and some T cell subsets that function as B cell helpers can be therapeutic targets of SLE. Mechanistic target of rapamycin (mTOR) signaling is implicated in the formation of B cells and germinal centers (GCs). We assessed the effect of metformin, which inhibits mTOR, on the development of autoimmunity using Roquin(san/san) mice. Oral administration of metformin inhibited the formation of splenic follicles and inflammation in kidney and liver tissues. It also decreased serum levels of anti-dsDNA Abs without affecting serum glucose levels. Moreover, metformin inhibited CD21(high) CD23(low) marginal zone B cells, B220(+)GL7(+) GC B cells, B220(-)CD138(+) PCs, and GC formation. A significant reduction in ICOS+ follicular helper T cells was found in the spleens of the metformin-treated group compared with the vehicle-treated group. In addition, metformin inhibited Th17 cells and induced regulatory T cells. These alterations in B and T cell subsets by metformin were associated with enhanced AMPK expression and inhibition of mTOR-STAT3 signaling. Furthermore, metformin induced p53 and NF erythroid-2-related factor-2 activity in splenic CD4(+) T cells. Taken together, metformin-induced alterations in AMPK-mTOR-STAT3 signaling may have therapeutic value in SLE by inhibiting B cell differentiation into PCs and GCs.</P>
IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis
Lee, Seon-Yeong,Jung, Young Ok,Kim, Doo-Jin,Kang, Chang-Min,Moon, Young-Mee,Heo, Yu-Jung,Oh, Hye-Jwa,Park, Seong-Jeong,Yang, Se-Hwan,Kwok, Seung Ki,Ju, Ji-Hyeon,Park, Sung-Hwan,Sung, Young Chul,Kim, H American Association of Immunologists 2015 Journal of Immunology Vol. No.
<P>IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)<SUB>2</SUB> subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist–knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)<SUB>2</SUB> on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)<SUB>2</SUB> model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)<SUB>2</SUB> inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4<SUP>+</SUP>CD25<SUP>+</SUP>Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor–related organ receptor γt and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)<SUB>2</SUB> suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling.</P>
IL-33–Induced Hematopoietic Stem and Progenitor Cell Mobilization Depends upon CCR2
Kim, Juyang,Kim, Wonyoung,Le, Hongnga T.,Moon, U J.,Tran, Vuvi G.,Kim, Hyun J.,Jung, Soyeon,Nguyen, Quang-Tam,Kim, Byung-Sam,Jun, Jae-Bum,Cho, Hong R.,Kwon, Byungsuk American Association of Immunologists 2014 Journal of Immunology Vol. No.
<P>IL-33 has been implicated in the pathogenesis of asthma, atopic allergy, anaphylaxis, and other inflammatory diseases by promoting the production of proinflammatory cytokines and chemokines or Th2 immune responses. In this study, we analyzed the in vivo effect of IL-33 administration. IL-33 markedly promoted myelopoiesis in the bone marrow and myeloid cell emigration. Concomitantly, IL-33 induced hematopoietic stem and progenitor cell (HSPC) mobilization and extramedullary hematopoiesis. HSPC mobilization was mediated mainly through increased levels of CCL7 produced by vascular endothelial cells in response to IL-33. In vivo treatment of IL-33 rapidly induced phosphorylation of ERK, JNK, and p38, and inhibition of these signaling molecules completely blocked the production of CCL7 induced by IL-33. Consistently, inhibitor of CCR2 markedly reduced IL-33–mediated HSPC mobilization in vivo and migration of HSPCs in response to CCL7 in vitro. IL-33–mobilized HSPCs were capable of homing to, and of long-term reconstitution in, the bone marrow of irradiated recipients. Immune cells derived from these recipients had normal antifungal activity. The ability of IL-33 to promote migration of HSPCs and myeloid cells into the periphery and to regulate their antifungal activity represents a previously unrecognized role of IL-33 in innate immunity. These properties of IL-33 have clinical implications in hematopoietic stem cell transplantation.</P>