Cathepsin G and Its Role in Inflammation and Autoimmune Diseases

Gao, Shu‐guang

doi:10.5606/archrheumatol.2018.6595

Cited by 75 publications

(57 citation statements)

References 73 publications

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“…In this regard, expression of Cathepsin G is northworthy since it is prominent serine protease that amplifies inflammation by stimulating the production of cytokines and chemokines that drive immune cell recruitment to the lung ( 59 ), and activates metalloproteases to cleave extracellular matrix proteins, thereby promoting neutrophil migration ( 60 ). Cathepsin G also induces potent chemotactic recruitment of monocytes, neutrophils and antigen presenting cells in addition to promoting endothelial and epithelial permeability ( 61 ). The latter function of Cathepsin G could be important in enhancing viral invasion to extra-alveolar sites while increased epithelial permeability might also explain the gastrointestinal route of transmission ( 12 ) (in review).…”

Section: Discussionmentioning

confidence: 99%

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

Rosa

Ahmed

Singh

et al. 2020

Preprint

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The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease or protection during COVID-19 severely hamper development of therapeutics and vaccines. Thus, the establishment of relevant animal models that mimic the pathobiology of the disease is urgent. Rhesus macaques infected with SARS-CoV-2 exhibit disease pathobiology similar to human COVID-19, thus serving as a relevant animal model. In the current study, we have characterized the transcriptional signatures induced in the lungs of juvenile and old rhesus macaques following SARS-CoV-2 infection. We show that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. We demonstrate that Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. In contrast, pathways involving VEGF are downregulated in lungs of old infected macaques. Using samples from humans with SARS-CoV-2 infection and COVID-19, we validate a subset of our findings. Finally, neutrophil degranulation, innate immune system and IFN gamma signaling pathways are upregulated in both tuberculosis and COVID-19, two pulmonary diseases where neutrophils are associated with increased severity. Together, our transcriptomic studies have delineated disease pathways to improve our understanding of the immunopathogenesis of COVID-19 to facilitate the design of new therapeutics for COVID-19.

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Section: Discussionmentioning

confidence: 99%

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

Rosa

Ahmed

Singh

et al. 2020

Preprint

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“…Cathepsin G is a serine protease mainly localized in the azurophilic granules of neutrophils (308, 309). With its proteolytic ability on cytokines, chemokines, cell surface proteins, extracellular matrices, outer membrane of infectant, angiotensin II, and proMMPs, cathepsin G exhibit important roles in inflammation, thrombogenesis, host defense, blood pressure, tumor invasion, and autoimmune diseases.…”

Section: Proteases In Pemphigoid Diseasesmentioning

confidence: 99%

Proteases in Pemphigoid Diseases

et al. 2019

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Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive treatments, which may be insufficient and are often associated with significant adverse events. As such, a deeper understanding of the pathomechanism(s) of pemphigoid diseases is necessary in order to identify improved therapeutic approaches. A major initiator of pemphigoid diseases is the accumulation of autoantibodies against proteins at the dermal-epidermal junction (DEJ), followed by protease activation at the lesion. The contribution of proteases to pemphigoid disease pathogenesis has been investigated using a combination of in vitro and in vivo models. These studies suggest proteolytic degradation of anchoring proteins proximal to the DEJ is crucial for dermal-epidermal separation and blister formation. In addition, proteases can also augment inflammation, expose autoantigenic cryptic epitopes, and/or provoke autoantigen spreading, which are all important in pemphigoid disease pathology. The present review summarizes and critically evaluates the current understanding with respect to the role of proteases in pemphigoid diseases.

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“…CTSG changes CXCL5 and chemokine (C-C motif) ligand 15 ( CCL15 ) into more potent chemotactic factors by a proteolytic processing. In addition, CTSG causes cell shape modification and intercellular gap formation in endothelial cell that increase endothelium permeability, supporting the migration of neutrophils, monocytes and antigen-presenting cells in the injured site [24]. CTSG affects also tissue remodelling directly by degrading components of the matrix and indirectly by cleaving and activating matrix metalloproteinases (MMPs), such as MMP1 and MMP2 [24].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Dermal Stem Cells of Diabetic Patients

Ferroni

Gardin

Paola

et al. 2019

Cells

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Diabetic foot ulcers (DFUs) are lesions that involve loss of epithelium and dermis, sometimes involving deep structures, compartments, and bones. The aim of this work is to investigate the innate regenerative properties of dermal tissue around ulcers by the identification and analysis of resident dermal stem cells (DSCs). Dermal samples were taken at the edge of DFUs, and genes related to the wound healing process were analyzed by the real-time PCR array. The DSCs were isolated and analyzed by immunofluorescence, flow cytometry, and real-time PCR array to define their stemness properties. The gene expression profile of dermal tissue showed a dysregulation in growth factors, metalloproteinases, collagens, and integrins involved in the wound healing process. In the basal condition, diabetic DSCs adhered on the culture plate with spindle-shaped fibroblast-like morphology. They were positive to the mesenchymal stem cells markers CD44, CD73, CD90, and CD105, but negative for the hematopoietic markers CD14, CD34, CD45, and HLA-DR. In diabetic DSCs, the transcription of genes related to self-renewal and cell division were equivalent to that in normal DSCs. However, the expression of CCNA2, CCND2, CDK1, ALDH1A1, and ABCG2 was downregulated compared with that of normal DSCs. These genes are also related to cell cycle progression and stem cell maintenance. Further investigation will improve the understanding of the molecular mechanisms by which these genes together govern cell proliferation, revealing new strategies useful for future treatment of DFUs.

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Cathepsin G and Its Role in Inflammation and Autoimmune Diseases

Cited by 75 publications

References 73 publications

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

Proteases in Pemphigoid Diseases

Characterization of Dermal Stem Cells of Diabetic Patients

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