Rebamipide attenuates autoimmune arthritis severity in SKG mice via regulation of B cell and antibody production

Byun, Jae Kyung; Moon, Su‐Jin; Jhun, Joo Yeon; Kim, E.-K.; Park, J.-S.; Youn, Jeehee; Min, Jun Ki; Park, S.-H.; Kim, H.-Y.; Cho, M.-L.

doi:10.1111/cei.12355

Cited by 18 publications

(14 citation statements)

References 42 publications

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“…TFH cells promote an immune response, while Breg cells inhibit an immune response. Rebampide treatment reduced the number of TFH cells, but increased the number of Breg cells, similar to our results. However, one study reported that TFH cells promoted IL‐10 production during the differentiation of Breg cells in systemic lupus erythematosus .…”

Section: Discussionsupporting

confidence: 91%

A higher frequency of IL‐10‐producing B cells in Hepatitis B virus‐associated membranous nephropathy

Liu

Wang

et al. 2016

Clin Exp Pharma Physio

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The purpose of this study is to elucidate the potential role of interleukin (IL)-10(+) regulatory B cells and other B cell subsets in the development of hepatitis B virus-associated membranous nephropathy (HBV-MN). A total of 14 patients with new onset HBV-MN, 12 individuals with immune-tolerant HBV infection (HBV-IT), and 12 healthy controls (HC) were examined for the percentages of CD38(+) , CD86(+) , CD27(+) , CD95(+) and IL-10(+) B cells by flow cytometry. Serum IL-10 concentration was examined by enzyme-linked immunosorbent assay (ELISA). The percentages of CD38(+) CD19(+) , CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , and CD95(+) CD19(+) B cells were significantly higher in HBV-MN patients than the HBV-IT and HC. The percentages of CD5(+) CD19(+) , IL-10(+) CD19(+) B cells and serum IL-10 level in HBV-MN patients were significantly higher than the HC, and lower than the HBV-IT. Percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells were reduced after treatment, while the percentages of CD5(+) CD1d(+) CD19(+) , CD5(+) CD1d(+) IL-10(+) CD19(+) , and IL-10(+) CD19(+) B cells were increased. The 24 h urinary protein concentration was positively correlated with the percentage of CD38(+) CD19(+) , and negatively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Similarly, the value of eGFR was negatively correlated with the percentage of CD38(+) CD19(+) , and positively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Serum IL-10 level and the percentage of IL-10(+) CD19(+) were negatively correlated with the percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells. These results suggest that CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , CD95(+) CD19(+) , and especially CD38(+) CD19(+) and IL-10(+) CD19(+) cells may participate in the pathogenesis of HBV-MN.

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Section: Discussionsupporting

confidence: 91%

A higher frequency of IL‐10‐producing B cells in Hepatitis B virus‐associated membranous nephropathy

Liu

Wang

et al. 2016

Clin Exp Pharma Physio

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“…Interestingly, a recent study showed that adjunct rebamipide therapy is also effective for preventing the occurrence of peptic ulcers in arthritic patients that are taking a COX-2-selective inhibitor [ 39 ]. It has been demonstrated that oral administration of rebamipide can reduce the clinical and histologic scores in animal models of rheumatoid arthritis, including collagen-induced arthritis and SKG mice [ 40 , 41 ]. There has been only one recent report regarding the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced rat knee OA [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis

Izawa¹,

Mori²,

Shinohara³

et al. 2016

PLoS ONE

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Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive degradation of cartilage and changes in subchondral bone. It is also one of the most serious subgroups of temporomandibular disorders. Rebamipide is a gastroprotective agent that is currently used for the treatment of gastritis and gastric ulcers. It scavenges reactive oxygen radicals and has exhibited anti-inflammatory potential. The aim of this study was to investigate the impact of rebamipide both in vivo and in vitro on the development of cartilage degeneration and osteoclast activity in an experimental murine model of TMJ-OA, and to explore its mode of action. Oral administration of rebamipide (0.6 mg/kg and 6 mg/kg) was initiated 24 h after TMJ-OA was induced, and was maintained daily for four weeks. Rebamipide treatment was found to attenuate cartilage degeneration, to reduce the number of apoptotic cells, and to decrease the expression levels of matrix metalloproteinase-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in TMJ-OA cartilage in a dose-dependent manner. Rebamipide also suppressed the activation of transcription factors (e.g., NF-κB, NFATc1) and mitogen-activated protein kinases (MAPK) by receptor activator of nuclear factor kappa-B ligand (RANKL) to inhibit the differentiation of osteoclastic precursors, and disrupted the formation of actin rings in mature osteoclasts. Together, these results demonstrate the inhibitory effects of rebamipide on cartilage degradation in experimentally induced TMJ-OA. Furthermore, suppression of oxidative damage, restoration of extracellular matrix homeostasis of articular chondrocytes, and reduced subchondral bone loss as a result of blocked osteoclast activation suggest that rebamipide is a potential therapeutic strategy for TMJ-OA.

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“…The inhibitor of Breg cells proliferation was reported as a suppressive factor of arthritis severity in RA murine model [35]. In this study, GCB cells expressing GL-7 are involved with the B cell immune response and Tfh cells revealing ICOS and PD-1 are involved in the germinal center responses.…”

Section: Q15mentioning

confidence: 67%

Coenzyme Q10 suppresses Th17 cells and osteoclast differentiation and ameliorates experimental autoimmune arthritis mice

et al. 2015

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Rebamipide attenuates autoimmune arthritis severity in SKG mice via regulation of B cell and antibody production

Cited by 18 publications

References 42 publications

A higher frequency of IL‐10‐producing B cells in Hepatitis B virus‐associated membranous nephropathy

A higher frequency of IL‐10‐producing B cells in Hepatitis B virus‐associated membranous nephropathy

Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis

Coenzyme Q10 suppresses Th17 cells and osteoclast differentiation and ameliorates experimental autoimmune arthritis mice

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