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1.
PLoS One ; 16(4): e0249340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793647

RESUMO

Many human viruses, including Epstein-Barr virus (EBV), do not infect mice, which is challenging for biomedical research. We have previously reported that EBV infection induces erosive arthritis, which histologically resembles rheumatoid arthritis, in humanized NOD/Shi-scid/IL-2Rγnull (hu-NOG) mice; however, the underlying mechanisms are not known. Osteoclast-like multinucleated cells were observed during bone erosion in this mouse model, and therefore, we aimed to determine whether the human or mouse immune system activated bone erosion and analyzed the characteristics and origin of the multinucleated cells in hu-NOG mice. Sections of the mice knee joint tissues were immunostained with anti-human antibodies against certain osteoclast markers, including cathepsin K and matrix metalloproteinase-9 (MMP-9). Multinucleated cells observed during bone erosion stained positively for human cathepsin K and MMP-9. These results indicate that human osteoclasts primarily induce erosive arthritis during EBV infections. Human osteoclast development from hematopoietic stem cells transplanted in hu-NOG mice remains unclear. To confirm their differentiation potential into human osteoclasts, we cultured bone marrow cells of EBV-infected hu-NOG mice and analyzed their characteristics. Multinucleated cells cultured from the bone marrow cells stained positive for human cathepsin K and human MMP-9, indicating that bone marrow cells of hu-NOG mice could differentiate from human osteoclast progenitor cells into human osteoclasts. These results indicate that the human immune response to EBV infection may induce human osteoclast activation and cause erosive arthritis in this mouse model. Moreover, this study is the first, to our knowledge, to demonstrate human osteoclastogenesis in humanized mice. We consider that this model is useful for studying associations of EBV infections with rheumatoid arthritis and human bone metabolism.


Assuntos
Artrite/patologia , Diferenciação Celular , Herpesvirus Humano 4/fisiologia , Osteogênese , Animais , Artrite/metabolismo , Artrite/virologia , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/virologia , Catepsina K/imunologia , Catepsina K/metabolismo , Modelos Animais de Doenças , Humanos , Subunidade gama Comum de Receptores de Interleucina/deficiência , Subunidade gama Comum de Receptores de Interleucina/genética , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Metaloproteinase 9 da Matriz/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Camundongos Transgênicos , Osteoclastos/citologia , Osteoclastos/metabolismo , Microtomografia por Raio-X
2.
Cell Prolif ; 53(1): e12722, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31737959

RESUMO

OBJECTIVES: The mechanisms underlying the effects of Toll-like receptor 9 (TLR9) and autophagy on rheumatoid arthritis (RA)-aggravated periodontitis are unclear. We aimed to explore a novel target, cathepsin K (Ctsk)-mediated TLR9-related autophagy, during the progress of periodontitis with RA. MATERIALS AND METHODS: DBA/J1 mouse model of periodontitis with RA was created by local colonization of Porphyromonas gingivalis (Pg) and injection of collagen. The expression of Ctsk was inhibited by adeno-associated virus (AAV). Micro-CT, immunohistochemistry (IHC), Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of TLR9-related autophagy in periodontitis with RA. Small interfering RNA (siRNA) and CpG oligodeoxynucleotides (CpG ODN) were applied in macrophages. Western blot, immunofluorescence (IF) and qRT-PCR were used to verify the in vivo results. RESULTS: RA can promote periodontitis bone destruction in the lesion area, while inhibiting Ctsk could effectively alleviate this effect. The infiltration of macrophages, TLR9, autophagy proteins (TFEB and LC3) and inflammatory cytokines increased in the periodontitis-with-RA group and was reduced by the inhibition of Ctsk in the periodontal region. Macrophage stimulation confirmed the in vivo results. With the activation of TLR9 by CpG ODN, inhibition of Ctsk could suppress both TLR9 downstream signalling proteins and autophagy-related proteins. CONCLUSIONS: This study advanced a novel role for Ctsk in TLR9 and autophagy to explain the interaction between periodontitis and RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Catepsina K/antagonistas & inibidores , Regulação para Baixo/efeitos dos fármacos , Oligodesoxirribonucleotídeos/farmacologia , Periodontite/tratamento farmacológico , Receptor Toll-Like 9/imunologia , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/imunologia , Catepsina K/genética , Catepsina K/imunologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos DBA , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/imunologia , Oligodesoxirribonucleotídeos/genética , Periodontite/genética , Periodontite/imunologia , Periodontite/patologia , Receptor Toll-Like 9/genética
3.
Front Immunol ; 10: 2558, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736973

RESUMO

A previously unreported population of foam cells (foamy macrophages) accumulates in the invasive fibrotic meninges during gap regeneration of transected adult Axolotl spinal cord (salamander Ambystoma mexicanum) and may act beneficially. Multinucleated giant cells (MNGCs) also occurred in the fibrotic meninges. Actin-label localization and transmission electron microscopy showed characteristic foam cell and MNGC podosome and ruffled border-containing sealing ring structures involved in substratum attachment, with characteristic intermediate filament accumulations surrounding nuclei. These cells co-localized with regenerating cord ependymal cell (ependymoglial) outgrowth. Phase contrast-bright droplets labeled with Oil Red O, DiI, and DyRect polar lipid live cell label showed accumulated foamy macrophages to be heavily lipid-laden, while reactive ependymoglia contained smaller lipid droplets. Both cell types contained both neutral and polar lipids in lipid droplets. Foamy macrophages and ependymoglia expressed the lipid scavenger receptor CD36 (fatty acid translocase) and the co-transporter toll-like receptor-4 (TLR4). Competitive inhibitor treatment using the modified fatty acid Sulfo-N-succinimidyl Oleate verified the role of the lipid scavenger receptor CD36 in lipid uptake studies in vitro. Fluoromyelin staining showed both cell types took up myelin fragments in situ during the regeneration process. Foam cells took up DiI-Ox-LDL and DiI-myelin fragments in vitro while ependymoglia took up only DiI-myelin in vitro. Both cell types expressed the cysteine proteinase cathepsin K, with foam cells sequestering cathepsin K within the sealing ring adjacent to the culture substratum. The two cell types act as sinks for Ox-LDL and myelin fragments within the lesion site, with foamy macrophages showing more Ox-LDL uptake activity. Cathepsin K activity and cellular localization suggested that foamy macrophages digest ECM within reactive meninges, while ependymal cells act from within the spinal cord tissue during outgrowth into the lesion site, acting in complementary fashion. Small MNGCs also expressed lipid transporters and showed cathepsin K activity. Comparison of 3H-glucosamine uptake in ependymal cells and foam cells showed that only ependymal cells produce glycosaminoglycan and proteoglycan-containing ECM, while the cathepsin studies showed both cell types remove ECM. Interaction of foam cells and ependymoglia in vitro supported the dispersion of ependymal outgrowth associated with tissue reconstruction in Axolotl spinal cord regeneration.


Assuntos
Ambystoma mexicanum/imunologia , Epêndima/citologia , Epêndima/imunologia , Células Espumosas/imunologia , Meninges/citologia , Meninges/imunologia , Regeneração da Medula Espinal/imunologia , Ambystoma mexicanum/metabolismo , Animais , Catepsina K/imunologia , Feminino , Masculino , Bainha de Mielina/metabolismo , Medula Espinal/imunologia
4.
Fish Shellfish Immunol ; 93: 153-160, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319206

RESUMO

Cathepsins are the best-known group of proteases in lysosomes, playing a significant role in immune responses. Cathepsin K (CTSK) is abundantly and selectively expressed in osteoclasts, dendritic cells and monocyte-derived macrophages, where it is involved in ECM degradation and bone remodeling. A growing body of evidences have indicated the vital roles of cathepsin K in innate immune responses. Here, one CTSK gene was captured in turbot (SmCTSK) with a 993 bp open reading frame (ORF). The genomic structure analysis showed that SmCTSK had 7 exons similar to other vertebrate species. The syntenic analysis revealed that CTSK had the same neighboring genes across all the selected species, which suggested the synteny encompassing CTSK region was conserved during vertebrate evolution. Subsequently, SmCTSK was widely expressed in all the examined tissues, with the highest expression level in spleen and the lowest expression level in liver. In addition, SmCTSK was significantly down-regulated in intestine following Gram-negative bacteria Vibrio anguillarum immersion challenge, but up-regulated in three tissues (gill, skin and intestine) following Gram-positive bacteria Streptococcus iniae immersion challenge. Finally, the rSmCTSK showed strong binding ability to all the examined microbial ligands. Taken together, our results suggested SmCTSK played vital roles in fish innate immune responses against infection. However, the knowledge of SmCTSK is still limited in teleost species, further studies should be carried out to better characterize its comprehensive roles in teleost mucosal immunity.


Assuntos
Catepsina K/genética , Catepsina K/imunologia , Doenças dos Peixes/imunologia , Linguados/genética , Linguados/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Animais , Catepsina K/química , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Filogenia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Streptococcus iniae/fisiologia , Vibrio/fisiologia , Vibrioses/imunologia , Vibrioses/veterinária
5.
J Dermatol ; 45(3): 252-263, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29226571

RESUMO

Psoriasis is an inflammatory skin disorder that includes dynamic interactions between the immune system and skin and is clinically characterized by keratinocyte proliferation and distinct inflammatory cell infiltrates. Cross-talk between keratinocytes and immunocytes is essential for the development of psoriasis given that it mediates the production of cytokines, chemokines and growth factors. To resolve the pathogenesis of psoriasis, numerous experimental animal models have been generated. In this review, we discuss recent findings from mouse models, their relevancy to psoriasis and use, including the discovery of new therapies.


Assuntos
Modelos Animais de Doenças , Queratinócitos/imunologia , Camundongos , Psoríase/imunologia , Pele/imunologia , Proteína ADAM17/antagonistas & inibidores , Proteína ADAM17/imunologia , Animais , Catepsina K/imunologia , Fármacos Dermatológicos/uso terapêutico , Humanos , Interleucinas/antagonistas & inibidores , Interleucinas/imunologia , Queratinócitos/metabolismo , Terapia de Alvo Molecular/métodos , Psoríase/tratamento farmacológico , Psoríase/patologia , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/imunologia , Pele/citologia , Pele/metabolismo , Especificidade da Espécie , Interleucina 22
6.
J Leukoc Biol ; 101(5): 1233-1243, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28196851

RESUMO

Inflammation-induced bone destruction is a major treatment target in many inflammatory skeletal diseases. The aim of this study was to investigate if the cysteine proteinase inhibitors cystatin C, fungal cysteine proteinase inhibitor (E-64), and N-benzyloxycarbonyl-arginyl-leucyl-valyl-glycyl-diazomethane acetate (Z-RLVG-CHN2) can inhibit LPS-induced osteoclast formation. Mouse bone marrow macrophages (BMMs) were isolated and primed with receptor activator of NF-κB ligand (RANKL) for 24 h, followed by stimulation with LPS, with and without inhibitors. Adult mice were injected locally with LPS and then treated with E-64 and osteoclast formation assessed by the number of cathepsin K+ multinucleated cells. Cystatin C inhibited LPS-induced osteoclast formation time and concentration dependently (IC50 = 0.3 µM). The effect was associated with decreased mRNA and protein expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K and of the osteoclastogenic transcription factors c-Fos and NFATc1. LPS-induced osteoclast formation on bone slices was also inhibited by cystatin C, resulting in decreased pit formation and release of bone matrix proteins. Similar data were obtained with E-64 and Z-RLVG-CHN2 Cystatin C was internalized in BMMs stimulated by LPS but not in unstimulated BMMs. Osteoclast formation induced by LPS was dependent on TNF-α, and the 3 inhibitors abolished LPS-induced TNF superfamily 2 (gene encoding TNF-α; Tnfsf2) mRNA expression without affecting Il1b, Il6, or oncostatin M (Osm) expression. Formation of osteoclasts in the skull bones after local LPS stimulation was inhibited by E-64. It is concluded that cysteine proteinase inhibitors effectively inhibit LPS-induced osteoclast formation in vivo and in vitro by inhibition of TNF-α expression. The targeting of cysteine proteinases might represent a novel treatment modality for prevention of inflammatory bone loss.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/prevenção & controle , Cistatina C/farmacologia , Inibidores de Cisteína Proteinase/farmacologia , Leucina/análogos & derivados , Oligopeptídeos/farmacologia , Osteoclastos/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/genética , Reabsorção Óssea/imunologia , Catepsina K/genética , Catepsina K/imunologia , Relação Dose-Resposta Imunológica , Regulação da Expressão Gênica , Interleucina-6/genética , Interleucina-6/imunologia , Leucina/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/imunologia , Oncostatina M/genética , Oncostatina M/imunologia , Osteoclastos/imunologia , Osteoclastos/patologia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/imunologia , Ligante RANK/antagonistas & inibidores , Ligante RANK/farmacologia , Transdução de Sinais , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
7.
Biomed Res Int ; 2014: 309718, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25587532

RESUMO

Cysteine cathepsins are a group of enzymes normally found in the endolysosomes where they are primarily involved in intracellular protein turnover but also have a critical role in MHC II-mediated antigen processing and presentation. However, in a number of pathologies cysteine cathepsins were found to be heavily upregulated and secreted into extracellular milieu, where they were found to degrade a number of extracellular proteins. A major role in modulating cathepsin activities play glycosaminoglycans, which were found not only to facilitate their autocatalytic activation including at neutral pH, but also to critically modulate their activities such as in the case of the collagenolytic activity of cathepsin K. The interaction between cathepsins and glycosaminoglycans will be discussed in more detail.


Assuntos
Apresentação de Antígeno/imunologia , Cisteína/imunologia , Glicosaminoglicanos/imunologia , Catepsina K/imunologia , Catepsina K/metabolismo , Cisteína/metabolismo , Genes MHC da Classe II/imunologia , Glicosaminoglicanos/metabolismo , Humanos , Lisossomos/imunologia , Lisossomos/metabolismo
8.
J Immunol ; 190(9): 4805-11, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23543761

RESUMO

Cathepsins (CTSs) are lysosomal cysteine proteases that play an important role in the turnover of intracellular proteins and extracellular proteins, such as the degradation of extracellular matrices and the processing of antigenic proteins. A CTS inhibitor, NC-2300, not only suppresses bone erosion by inhibition of cathepsin K (CTSK), but also ameliorates paw swelling at inflamed joints in adjuvant-induced arthritis in rats. It has been demonstrated that the amelioration of joint inflammation by NC-2300 is mediated by the downregulation of cytokine expression in dendritic cells, which are essential for Th17 activation. In this work, we studied the role for CTSs in the pathogenesis of psoriasis-like lesion in K5.Stat3C mice, a mouse model of psoriasis, in which Th17 contributes to lesion development similar to psoriasis. Psoriatic lesions expressed increased levels of Ctsk and Ctss mRNA compared with uninvolved skin and normal control skin. Similarly, the epidermis and dermis in K5.Stat3C mice demonstrated increased CTSK activities, which were sensitive to NC-2300. Topical treatment with NC-2300 significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like lesions in K5.Stat3C mice, and downregulated the expression of IL-12, IL-23, and Th17 cytokines. In vitro experiments revealed that TLR7 activation of bone marrow-derived myeloid dendritic cells led to increase in IL-23 at mRNA and protein levels, which were downregulated by NC-2300. These results suggest that CTSK plays a role in development of psoriatic lesions through TLR7-dependent Th17 polarization.


Assuntos
Catepsina K/metabolismo , Derme/enzimologia , Psoríase/enzimologia , Células Th17/enzimologia , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/metabolismo , Animais , Medula Óssea/imunologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Catepsina K/genética , Catepsina K/imunologia , Derme/imunologia , Derme/patologia , Regulação para Baixo , Epiderme/enzimologia , Epiderme/imunologia , Epiderme/patologia , Feminino , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-12/metabolismo , Interleucina-23/genética , Interleucina-23/imunologia , Interleucina-23/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/imunologia , Células Mieloides/metabolismo , Células Mieloides/patologia , Psoríase/genética , Psoríase/imunologia , Psoríase/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Th17/imunologia , Células Th17/patologia , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/imunologia , Receptor 8 Toll-Like/genética , Receptor 8 Toll-Like/imunologia
9.
Exp Lung Res ; 37(7): 408-18, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21721952

RESUMO

Cathepsin K (CatK) is a potent collagenase and elastase and may be involved in the development of neonatal bronchopulmonary dysplasia. The authors evaluated the effects of CatK deletion on neonatal lung development and response to prolonged hyperoxic challenge. CatK deficiency resulted in thinner alveolar walls than wild-type littermates on postnatal day (PN) 7. However, no morphological difference could be detected between CatK-deficient and control groups on PN 14. Exposure to 90% oxygen for 7 days after birth caused intensive CatK expression in the bronchial epithelium and alveolar macrophages of wild-type mice. Hyperoxia caused fatal respiratory distress in both groups of mice. However, whereas ∼20% of wild-type mice survived for 2 weeks in hyperoxia, all CatK-deficient mice died within the first 9 postnatal days. Hyperoxia-exposed lungs of CatK-deficient mice contained high number of macrophages and multinucleated giant cells and had increased content of reduced glutathione, indicating intensified pulmonary oxidative stress. These results suggest that CatK is involved in pulmonary development and it may be an important host-defence protease in the oxygen-stressed newborn lung.


Assuntos
Catepsina K/deficiência , Catepsina K/fisiologia , Hiperóxia/complicações , Lesão Pulmonar/etiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Catepsina K/imunologia , Pulmão/crescimento & desenvolvimento , Pulmão/patologia , Macrófagos Alveolares , Camundongos , Estresse Oxidativo , Alvéolos Pulmonares
10.
Arthritis Rheum ; 63(5): 1365-75, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21337316

RESUMO

OBJECTIVE: Rheumatoid arthritis, which is associated with elevated levels of S100A8 and S100A9, is characterized by severe bone erosions caused by enhanced osteoclast formation and activity. The aim of the present study was to investigate the role of S100A8 and S100A9 in osteoclastic bone destruction in murine antigen-induced arthritis (AIA). METHODS: Bone destruction was analyzed in the arthritic knee joints of S100A9-deficient mice in which S100A8 protein expression was also lacking, and in wild-type (WT) controls. Osteoclast precursors from S100A9-deficient and WT mice were differentiated into osteoclasts in vitro. Additionally, precursors were stimulated with S100A8, S100A9, or S100A8/A9 during osteoclastogenesis. Receptor involvement was investigated using an anti-receptor for advanced glycation end products (anti-RAGE)-blocking antibody, soluble RAGE, or Toll-like receptor 4 (TLR-4)-deficient osteoclast precursors. The formation of osteoclasts and actin rings, the regulation of osteoclast markers, and bone resorption were analyzed. RESULTS: Bone erosions and cathepsin K staining were significantly suppressed in S100A9-deficient mice after AIA induction. However, osteoclast precursors from S100A9-deficient mice developed normally into functional osteoclasts, which excludes a role for intrinsic S100A8/A9. In contrast to the results observed with S100A9 and S100A8/A9, the addition of S100A8 during osteoclastogenesis resulted in stimulation of osteoclast formation in conjunction with enhanced actin ring formation and increased bone resorption. Analysis of the putative receptor for S100A8 in osteoclastogenesis revealed that osteoclast differentiation and function could not be inhibited by blocking RAGE, whereas the increase in osteoclast numbers and enhanced bone resorption were completely abrogated using TLR-4-deficient osteoclast precursors. CONCLUSION: These results demonstrate that S100A8 stimulated osteoclast formation and activity and suggest that both S100A8 and TLR-4 are important factors in mediating osteoclastic bone destruction in experimental arthritis.


Assuntos
Artrite Experimental/metabolismo , Reabsorção Óssea/metabolismo , Calgranulina A/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Artrite Experimental/genética , Artrite Experimental/imunologia , Reabsorção Óssea/genética , Reabsorção Óssea/imunologia , Osso e Ossos/imunologia , Osso e Ossos/metabolismo , Calgranulina A/genética , Calgranulina A/imunologia , Catepsina K/imunologia , Catepsina K/metabolismo , Articulação do Joelho/imunologia , Articulação do Joelho/metabolismo , Camundongos , Camundongos Knockout , Osteoclastos/imunologia , Osteoclastos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia
11.
Fish Shellfish Immunol ; 28(4): 511-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20025977

RESUMO

The innate immunity and expression profiles of cathepsins D were determined in the goldfish (Carassius auratus) tissues after challenge with a fish pathogen Aeromonas hydrophila. The innate immunity of reactive oxygen species (ROS) and reactive nitrogen species (RNS) were determined by peripheral blood leucocytes. Blood and tissue samples of the muscle, gills, liver, kidney, heart, spleen, and intestine were sampled at 1, 3, 6 and 12 h post-infection for cathepsin D expression by semi-quantitative RT-PCR. The ROS and RNS production did not significantly increase at 1 h post-challenged goldfish. However, the ROS and RNS production was significantly increased after 3 h post-challenged fish compared to the control. The cathepsin D expression was found very low in muscle and kidney of the control fish, other tissues was not found the expression. A similar pattern was found in goldfish at 1 h post-challenge with A. hydrophila. However, at 3 h post-challenge goldfish, the cathepsin D expression was high only in the heart. At 6 h post-challenge goldfish, the cathepsin D expression was seen high all the tissues, except in the spleen. However, the expression was decreased at 12 h post-infection samples. This result was suggested that the goldfish infected with A. hydrophila decreased the innate immunity level in peripheral blood and expressed the cathepsin D in tissues.


Assuntos
Aeromonas hydrophila/imunologia , Catepsina K/imunologia , Doenças dos Peixes/imunologia , Carpa Dourada/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunidade Inata , Animais , Doenças dos Peixes/microbiologia , Doenças dos Peixes/mortalidade , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/mortalidade , Espécies Reativas de Oxigênio/imunologia
12.
Immunology ; 128(1 Suppl): e315-24, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19019090

RESUMO

Formation of osteoclasts and consequent joint destruction are hallmarks of rheumatoid arthritis (RA). Here we show that LIGHT, a member of the tumour necrosis factor (TNF) superfamily, induced the differentiation into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) of CD14(+) monocytes cocultured with nurse-like cells isolated from RA synovium, but not of freshly isolated CD14(+) monocytes. Receptor activator of nuclear factor-kappaB ligand (RANKL) enhanced this LIGHT-induced generation of TRAP-positive MNCs. The MNCs showed the phenotypical and functional characteristics of osteoclasts; they showed the expression of osteoclast markers such as cathepsin K, actin-ring formation, and the ability to resorb bone. Moreover, the MNCs expressed both matrix metalloproteinase 9 (MMP-9) and MMP-12, but the latter was not expressed in osteoclasts induced from CD14(+) monocytes by RANKL. Immunohistochemical analysis showed that the MMP-12-producing MNCs were present in the erosive areas of joints in RA, but not in the affected joints of osteoarthritic patients. These findings suggested that LIGHT might be involved in the progression of inflammatory bone destruction in RA, and that osteoclast progenitors might become competent for LIGHT-mediated osteoclastogenesis via interactions with synoviocyte-like nurse-like cells.


Assuntos
Artrite Reumatoide/imunologia , Monócitos/imunologia , Osteoclastos/imunologia , Membrana Sinovial/imunologia , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/fisiologia , Fosfatase Ácida/efeitos dos fármacos , Fosfatase Ácida/imunologia , Fosfatase Ácida/metabolismo , Artrite Reumatoide/metabolismo , Reabsorção Óssea/imunologia , Reabsorção Óssea/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/imunologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Catepsina K/efeitos dos fármacos , Catepsina K/imunologia , Catepsina K/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Humanos , Isoenzimas/efeitos dos fármacos , Isoenzimas/imunologia , Isoenzimas/metabolismo , Metaloproteinase 12 da Matriz/efeitos dos fármacos , Metaloproteinase 12 da Matriz/imunologia , Metaloproteinase 12 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Ligante RANK/farmacologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Fosfatase Ácida Resistente a Tartarato , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/farmacologia
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