The Experts below are selected from a list of 933 Experts worldwide ranked by ideXlab platform

K. Nishida - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of histone deacetylase down-regulates the expression of hypoxia-induced vascular endothelial growth factor by rheumatoid synovial fibroblasts
    Inflammation Research, 2008
    Co-Authors: Hiroaki Manabe, S. Miyazawa, T. Komiyama, A. Kitamura, Takayuki Furumatsu, Yoshifumi Ninomiya, Hiroshi Asahara, Y. Nasu, T. Ozaki, K. Nishida
    Abstract:

    Objective: To investigate the effect of FK228 on the in vitro expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) by rheumatoid Arthritis synovial fibroblasts (RASFs), and on the in vivo expression of VEGF and angiogenesis in the synovial tissue of mice with Collagen-Antibody-Induced Arthritis (CAIA). Methods: RASFs were stimulated with IL-1β and TNFα and then incubated under hypoxia (1 % O_2) with various concentrations of FK228. The effects of FK228 on the expression of HIF-1α and VEGF mRNA were examined by quantitative real-time PCR. Changes in HIF-1α protein expression and the secretion of VEGF protein into the culture medium were examined by Western blot analysis and ELISA, respectively. Immunohistochemical analysis was carried out to investigate the expression and distribution of VEGF in synovial tissues of CAIA mice. Results: The cytokine-stimulated expression of HIF-1α and VEGF mRNA was inhibited by FK228 in a dose-dependent manner. FK228 also reduced the expression of HIF-1α and VEGF protein. Intravenous administration of FK228 (2.5 mg/kg) suppressed VEGF expression, and also blocked angiogenesis in the synovial tissue of CAIA. Conclusion: FK228 may exhibit a therapeutic effect on RA by inhibition of angiogenesis through down-regulation of angiogenesis related factors, HIF-1α and VEGF.

  • Novel transdermal photodynamic therapy using ATX-S10·Na(II) induces apoptosis of synovial fibroblasts and ameliorates Collagen Antibody-Induced Arthritis in mice
    Rheumatology International, 2005
    Co-Authors: S. Miyazawa, K. Nishida, T. Komiyama, Y. Nakae, K. Takeda, M. Yorimitsu, A. Kitamura, T. Kunisada, A. Ohtsuka, H. Inoue
    Abstract:

    We aimed to test the effect of transdermal photodynamic therapy (PDT) on synovial proliferation in vitro and in vivo, using a novel photosensitizer, ATX-S10·Na(II). Synovial fibroblasts were obtained from patients with RA (RASF). Cell viability with or without PDT was determined by MTT assay. Cell morphology was examined by light and transmission electron microscopy. DNA fragmentation was labeled by TUNEL stain. Collagen Antibody-Induced Arthritis (CAIA) was induced in DBA/1 mice, and the effects of transdermal PDT were evaluated by clinical and histological examination. PDT showed drug concentration-dependent and laser dose-dependent cytotoxicity on RASF. TUNEL stain and TEM study revealed the induction of apoptotic cell death of RASF. Transdermal PDT significantly reduced clinical Arthritis and synovial inflammation in this model of Arthritis. These results suggest that transdermal PDT using ATX-S10·Na(II) might be a novel less invasive treatment strategy for small joint Arthritis and tenosynovitis.

Hiroaki Manabe - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of histone deacetylase down-regulates the expression of hypoxia-induced vascular endothelial growth factor by rheumatoid synovial fibroblasts.
    Inflammation Research, 2008
    Co-Authors: Hiroaki Manabe, A. Kitamura, Yoshihisa Nasu, Shinichi Miyazawa, Takamitsu Komiyama, Toshifumi Ozaki, Takayuki Furumatsu, Yoshifumi Ninomiya, Hiroshi Asahara, Keiichiro Nishida
    Abstract:

    Objective: To investigate the effect of FK228 on the in vitro expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) by rheumatoid Arthritis synovial fibroblasts (RASFs), and on the in vivo expression of VEGF and angiogenesis in the synovial tissue of mice with Collagen-Antibody-Induced Arthritis (CAIA).

  • Inhibition of histone deacetylase down-regulates the expression of hypoxia-induced vascular endothelial growth factor by rheumatoid synovial fibroblasts
    Inflammation Research, 2008
    Co-Authors: Hiroaki Manabe, S. Miyazawa, T. Komiyama, A. Kitamura, Takayuki Furumatsu, Yoshifumi Ninomiya, Hiroshi Asahara, Y. Nasu, T. Ozaki, K. Nishida
    Abstract:

    Objective: To investigate the effect of FK228 on the in vitro expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) by rheumatoid Arthritis synovial fibroblasts (RASFs), and on the in vivo expression of VEGF and angiogenesis in the synovial tissue of mice with Collagen-Antibody-Induced Arthritis (CAIA). Methods: RASFs were stimulated with IL-1β and TNFα and then incubated under hypoxia (1 % O_2) with various concentrations of FK228. The effects of FK228 on the expression of HIF-1α and VEGF mRNA were examined by quantitative real-time PCR. Changes in HIF-1α protein expression and the secretion of VEGF protein into the culture medium were examined by Western blot analysis and ELISA, respectively. Immunohistochemical analysis was carried out to investigate the expression and distribution of VEGF in synovial tissues of CAIA mice. Results: The cytokine-stimulated expression of HIF-1α and VEGF mRNA was inhibited by FK228 in a dose-dependent manner. FK228 also reduced the expression of HIF-1α and VEGF protein. Intravenous administration of FK228 (2.5 mg/kg) suppressed VEGF expression, and also blocked angiogenesis in the synovial tissue of CAIA. Conclusion: FK228 may exhibit a therapeutic effect on RA by inhibition of angiogenesis through down-regulation of angiogenesis related factors, HIF-1α and VEGF.

Rikard Holmdahl - One of the best experts on this subject based on the ideXlab platform.

  • Collagen antibody induced Arthritis
    Methods in molecular medicine, 2020
    Co-Authors: Kutty Selva Nandakumar, Rikard Holmdahl
    Abstract:

    Rheumatoid Arthritis (RA) is a polygenic and multifactorial disease. Many complex immunological and genetic interactions are involved in the final out come of the clinical disease. To understand the various disease pathways operating during the disease course, we need many different animal models. Collagen induced Arthritis (CIA) is one of the widely used animal models sharing many pathological and histological similarities with RA and antibodies play an important role in the inflammatory phase of CIA. This chapter describes, in detail, an animal model for Arthritis using CII specific monoclonal antibodies, the so-called Collagen antibody induced Arthritis (CAIA), which shares many characteristics of CIA. CAIA model provides an opportunity to study the inflammatory phase of Arthritis without involving the priming phase of the immune response. CAIA can be used for not only studying inflammatory processes in Arthritis and screening drug candidates controlling joint inflammatory phase but also as a model for studying common mechanisms involved in many antibody mediated diseases. (Less)

  • Efficient promotion of Collagen antibody induced Arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both Collagen induced Arthritis and rheumatoid Arthritis.
    Journal of immunological methods, 2020
    Co-Authors: Kutty Selva Nandakumar, Rikard Holmdahl
    Abstract:

    An antibody response to defined epitopes located on the triple helical portion of type II Collagen (CII) is associated with the development of Collagen-induced Arthritis (CIA) and rheumatoid Arthritis (RA). Monoclonal antibodies to epitopes associated with Arthritis, but not antibodies specific for epitopes not associated with Arthritis, induce Arthritis in mice, the so-called Collagen antibody induced Arthritis (CAIA) model. We have selected monoclonal IgG antibodies specific for four well-defined major epitopes on triple helical CII, the C1, J1, D3 and U1 epitopes. These antibodies bind the epitopes specifically as determined using recombinant or synthetic triple helical epitopes. They are encoded from somatically mutated V genes. They all bind cartilage in vivo in normal mice. All of the antibodies induce mild Arthritis after injection intravenously and if injected as a cocktail they induce severe clinical Arthritis. Intravenous injection of a total of 4 mg antibodies (0.5 mg antibodies per clone) induced Arthritis in several different mouse strains without any secondary immune stimulus and intraperitoneal injection of LPS 7 days later dramatically raised the severity. Thus, this method is recommended as a new protocol for the induction of CAIA.

  • Antibody-Induced Arthritis: disease mechanisms and genes involved at the effector phase of Arthritis
    Arthritis Research & Therapy, 2020
    Co-Authors: Kutty Selva Nandakumar, Rikard Holmdahl
    Abstract:

    During the development of rheumatoid Arthritis (RA) autoantibodies to IgG-Fc, citrullinated proteins, Collagen type II (CII), glucose 6 phosphoisomerase (G6PI) and some other self-antigens appear. Of these, a pathogenic effect of the anti-CII and anti-G6PI antibodies is well demonstrated using animal models. These new antibody mediated Arthritis models have proven to be very useful for studies involved in understanding the molecular pathways of the induction of Arthritis in joints. Both the complement and FcγR systems have been found to play essential roles. Neutrophils and macrophages are important inflammatory cells and the secretion of tumour necrosis factor-α and IL-1β is pathogenic. The identification of the genetic polymorphisms predisposing to Arthritis is important for understanding the complexity of Arthritis. Disease mechanisms and gene regions studied using the two Antibody-Induced Arthritis mouse models (Collagen Antibody-Induced Arthritis and serum transfer-induced Arthritis) are compared and discussed for their relevance in RA pathogenesis.

  • Collagen Antibody-Induced Arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency.
    Arthritis & Rheumatism, 2012
    Co-Authors: Jie Su, Kutty Selva Nandakumar, Rikard Holmdahl, Katalin Sandor, Nilesh M. Agalave, Johanna Lundberg, Simone Codeluppi, Azar Baharpoor, Camilla I. Svensson
    Abstract:

    Objective Pain is one of the most debilitating symptoms reported by rheumatoid Arthritis (RA) patients. While the Collagen antibody–induced Arthritis (CAIA) model is used for studying the effector phase of RA pathologic progression, it has not been evaluated as a model for studies of pain. Thus, this study was undertaken to examine pain-like behavior induced by antiCollagen antibodies and to assess the effect of currently prescribed analgesics for RA. In addition, the involvement of spinal glia in Antibody-Induced pain was explored. Methods CAIA was induced in mice by intravenous injection of a Collagen antibody cocktail, followed by intraperitoneal injection of lipopolysaccharide. Disease severity was assessed by visual and histologic examination. Pain-like behavior and the antinociceptive effect of diclofenac, buprenorphine, gabapentin, pentoxifylline, and JNK-interacting protein 1 were examined in mechanical stimulation experiments. Spinal astrocyte and microglia reactivity were investigated by real-time polymerase chain reaction and immunohistochemistry. Results Following the induction of CAIA, mice developed transient joint inflammation. In contrast, pain-like behavior was observed prior to, and outlasted, the visual signs of Arthritis. Whereas gabapentin and buprenorphine attenuated mechanical hypersensitivity during both the inflammatory and postinflammatory phases of Arthritis, diclofenac was antinociceptive only during the inflammatory phase. Spinal astrocytes and microglia displayed time-dependent signs of activation, and inhibition of glial activity reversed CAIA-induced mechanical hypersensitivity. Conclusion CAIA represents a multifaceted model for studies exploring the mechanisms of pain induced by inflammation in the articular joint. Our findings of a time-dependent prostaglandin and spinal glial contribution to Antibody-Induced pain highlight the importance of using appropriate disease models to assess joint-related pain.

  • Keratinocyte growth factor (KGF) delays the onset of Collagen-induced Arthritis
    Autoimmunity, 2012
    Co-Authors: Konstantin Yakimchuk, Kutty Selva Nandakumar, Rikard Holmdahl, Liying Chen, Sam Okret, Mikael Jondal
    Abstract:

    Background: Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family. KGF protects the oral and intestinal mucosa against damage induced by irradiation or chemotherapy. Previous studies have found the expression of KGF in chondrocytes and suggested that KGF promotes the wound healing process in injured cartilage. KGF also has important effects on the immune system such as the regeneration of thymus tissue and the formation of regulatory T cells (Treg) in the periphery. Aim: Here we investigated the effect of KGF on Collagen type II induced Arthritis (CIA) and anti-Collagen antibody induced Arthritis (CAIA) in order to discriminate between immunoregulatory effect and direct protective effect on chondrocytes. Methods: CIA was induced by immunization with CII and CAIA by treatment of mice with a cocktail of four different anti-CII antibodies. The effect of KGF on the thymus and spleen was analyzed by FACS and by immunohistochemistry. Results: We have found that KGF treatment delaye...

Keiichiro Nishida - One of the best experts on this subject based on the ideXlab platform.

  • Light and electron microscopic detection of inflammation-targeting liposomes encapsulating high-density colloidal gold in arthritic mice
    Inflammation Research, 2013
    Co-Authors: Ami Maehara, Keiichiro Nishida, Aiji Ohtsuka, Yoshifumi Ninomiya, Masumi Furutani, Emi Matsumoto, Toshitaka Oohashi
    Abstract:

    Objective We have previously demonstrated the efficient and time-dependent transvascular localization of Sialyl Lewis X (SLX)-liposomes to inflammatory sites, but the final target of the SLX-liposomes remained uncertain. The aim of this study was to identify the target cells of the liposomes within the inflamed joints of Collagen Antibody-Induced Arthritis (CAIA) model mice.

  • trichostatin a a histone deacetylase inhibitor suppresses synovial inflammation and subsequent cartilage destruction in a Collagen antibody induced Arthritis mouse model
    Osteoarthritis and Cartilage, 2008
    Co-Authors: Yoshihisa Nasu, Keiichiro Nishida, Shinichi Miyazawa, Takamitsu Komiyama, Yasutaka Kadota, Aki Yoshida, Satoshi Hirohata, Aiji Ohtsuka, Toshifumi Ozaki
    Abstract:

    Summary Objective To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a Collagen Antibody-Induced Arthritis (CAIA) mouse model. Methods CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0mg/kg) and various parameters were monitored for 14 days. On Day 15, the hind paws were examined histologically. To investigate the effects of TSA on the expressions of matrix metalloproteinase (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II Collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation. Results In the TSA-treated group, clinical Arthritis was significantly ameliorated in a dose-dependent manner. The severity of synovial inflammation and the cartilage destruction score were significantly lower in the TSA 2.0mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0mg/kg group than in the control group. In contrast, the number of TIMP-1-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0mg/kg group than in the control group. TSA suppressed interleukin 1-β and tumor necrosis factor-α-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5. Conclusion The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression.

  • Inhibition of histone deacetylase down-regulates the expression of hypoxia-induced vascular endothelial growth factor by rheumatoid synovial fibroblasts.
    Inflammation Research, 2008
    Co-Authors: Hiroaki Manabe, A. Kitamura, Yoshihisa Nasu, Shinichi Miyazawa, Takamitsu Komiyama, Toshifumi Ozaki, Takayuki Furumatsu, Yoshifumi Ninomiya, Hiroshi Asahara, Keiichiro Nishida
    Abstract:

    Objective: To investigate the effect of FK228 on the in vitro expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) by rheumatoid Arthritis synovial fibroblasts (RASFs), and on the in vivo expression of VEGF and angiogenesis in the synovial tissue of mice with Collagen-Antibody-Induced Arthritis (CAIA).

Kutty Selva Nandakumar - One of the best experts on this subject based on the ideXlab platform.

  • Collagen antibody induced Arthritis
    Methods in molecular medicine, 2020
    Co-Authors: Kutty Selva Nandakumar, Rikard Holmdahl
    Abstract:

    Rheumatoid Arthritis (RA) is a polygenic and multifactorial disease. Many complex immunological and genetic interactions are involved in the final out come of the clinical disease. To understand the various disease pathways operating during the disease course, we need many different animal models. Collagen induced Arthritis (CIA) is one of the widely used animal models sharing many pathological and histological similarities with RA and antibodies play an important role in the inflammatory phase of CIA. This chapter describes, in detail, an animal model for Arthritis using CII specific monoclonal antibodies, the so-called Collagen antibody induced Arthritis (CAIA), which shares many characteristics of CIA. CAIA model provides an opportunity to study the inflammatory phase of Arthritis without involving the priming phase of the immune response. CAIA can be used for not only studying inflammatory processes in Arthritis and screening drug candidates controlling joint inflammatory phase but also as a model for studying common mechanisms involved in many antibody mediated diseases. (Less)

  • Efficient promotion of Collagen antibody induced Arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both Collagen induced Arthritis and rheumatoid Arthritis.
    Journal of immunological methods, 2020
    Co-Authors: Kutty Selva Nandakumar, Rikard Holmdahl
    Abstract:

    An antibody response to defined epitopes located on the triple helical portion of type II Collagen (CII) is associated with the development of Collagen-induced Arthritis (CIA) and rheumatoid Arthritis (RA). Monoclonal antibodies to epitopes associated with Arthritis, but not antibodies specific for epitopes not associated with Arthritis, induce Arthritis in mice, the so-called Collagen antibody induced Arthritis (CAIA) model. We have selected monoclonal IgG antibodies specific for four well-defined major epitopes on triple helical CII, the C1, J1, D3 and U1 epitopes. These antibodies bind the epitopes specifically as determined using recombinant or synthetic triple helical epitopes. They are encoded from somatically mutated V genes. They all bind cartilage in vivo in normal mice. All of the antibodies induce mild Arthritis after injection intravenously and if injected as a cocktail they induce severe clinical Arthritis. Intravenous injection of a total of 4 mg antibodies (0.5 mg antibodies per clone) induced Arthritis in several different mouse strains without any secondary immune stimulus and intraperitoneal injection of LPS 7 days later dramatically raised the severity. Thus, this method is recommended as a new protocol for the induction of CAIA.

  • Antibody-Induced Arthritis: disease mechanisms and genes involved at the effector phase of Arthritis
    Arthritis Research & Therapy, 2020
    Co-Authors: Kutty Selva Nandakumar, Rikard Holmdahl
    Abstract:

    During the development of rheumatoid Arthritis (RA) autoantibodies to IgG-Fc, citrullinated proteins, Collagen type II (CII), glucose 6 phosphoisomerase (G6PI) and some other self-antigens appear. Of these, a pathogenic effect of the anti-CII and anti-G6PI antibodies is well demonstrated using animal models. These new antibody mediated Arthritis models have proven to be very useful for studies involved in understanding the molecular pathways of the induction of Arthritis in joints. Both the complement and FcγR systems have been found to play essential roles. Neutrophils and macrophages are important inflammatory cells and the secretion of tumour necrosis factor-α and IL-1β is pathogenic. The identification of the genetic polymorphisms predisposing to Arthritis is important for understanding the complexity of Arthritis. Disease mechanisms and gene regions studied using the two Antibody-Induced Arthritis mouse models (Collagen Antibody-Induced Arthritis and serum transfer-induced Arthritis) are compared and discussed for their relevance in RA pathogenesis.

  • Collagen Antibody-Induced Arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency.
    Arthritis & Rheumatism, 2012
    Co-Authors: Jie Su, Kutty Selva Nandakumar, Rikard Holmdahl, Katalin Sandor, Nilesh M. Agalave, Johanna Lundberg, Simone Codeluppi, Azar Baharpoor, Camilla I. Svensson
    Abstract:

    Objective Pain is one of the most debilitating symptoms reported by rheumatoid Arthritis (RA) patients. While the Collagen antibody–induced Arthritis (CAIA) model is used for studying the effector phase of RA pathologic progression, it has not been evaluated as a model for studies of pain. Thus, this study was undertaken to examine pain-like behavior induced by antiCollagen antibodies and to assess the effect of currently prescribed analgesics for RA. In addition, the involvement of spinal glia in Antibody-Induced pain was explored. Methods CAIA was induced in mice by intravenous injection of a Collagen antibody cocktail, followed by intraperitoneal injection of lipopolysaccharide. Disease severity was assessed by visual and histologic examination. Pain-like behavior and the antinociceptive effect of diclofenac, buprenorphine, gabapentin, pentoxifylline, and JNK-interacting protein 1 were examined in mechanical stimulation experiments. Spinal astrocyte and microglia reactivity were investigated by real-time polymerase chain reaction and immunohistochemistry. Results Following the induction of CAIA, mice developed transient joint inflammation. In contrast, pain-like behavior was observed prior to, and outlasted, the visual signs of Arthritis. Whereas gabapentin and buprenorphine attenuated mechanical hypersensitivity during both the inflammatory and postinflammatory phases of Arthritis, diclofenac was antinociceptive only during the inflammatory phase. Spinal astrocytes and microglia displayed time-dependent signs of activation, and inhibition of glial activity reversed CAIA-induced mechanical hypersensitivity. Conclusion CAIA represents a multifaceted model for studies exploring the mechanisms of pain induced by inflammation in the articular joint. Our findings of a time-dependent prostaglandin and spinal glial contribution to Antibody-Induced pain highlight the importance of using appropriate disease models to assess joint-related pain.

  • Keratinocyte growth factor (KGF) delays the onset of Collagen-induced Arthritis
    Autoimmunity, 2012
    Co-Authors: Konstantin Yakimchuk, Kutty Selva Nandakumar, Rikard Holmdahl, Liying Chen, Sam Okret, Mikael Jondal
    Abstract:

    Background: Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family. KGF protects the oral and intestinal mucosa against damage induced by irradiation or chemotherapy. Previous studies have found the expression of KGF in chondrocytes and suggested that KGF promotes the wound healing process in injured cartilage. KGF also has important effects on the immune system such as the regeneration of thymus tissue and the formation of regulatory T cells (Treg) in the periphery. Aim: Here we investigated the effect of KGF on Collagen type II induced Arthritis (CIA) and anti-Collagen antibody induced Arthritis (CAIA) in order to discriminate between immunoregulatory effect and direct protective effect on chondrocytes. Methods: CIA was induced by immunization with CII and CAIA by treatment of mice with a cocktail of four different anti-CII antibodies. The effect of KGF on the thymus and spleen was analyzed by FACS and by immunohistochemistry. Results: We have found that KGF treatment delaye...