Type XVIII collagen degradation products in acute lung injury

Perkins, Gavin D.; Nathani, Nazim; Richter, Alex; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, William; McAuley, Daniel F.; Gao, Fang; Thickett, David

doi:10.1186/cc7779

Cited by 12 publications

(8 citation statements)

References 33 publications

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“…However, given that the turnover of substrate was very low, we suspect that the majority of elastase may be present on the surface of airway neutrophils. 35 We also quantified levels of the endostatin which is a COOH-terminal fragment of collagen XVIII that can be generated by elastase and is upregulated in the BALF from a human in vivo LPS challenge model and acute 36,37 Although both WT-and GG-elafin inhibited the generation of endostatin in comparison to the LPS alone group, only the GG-elafin was significantly lower compared to LPS alone, which correlates well with our neutrophil counts.…”

Section: Discussionsupporting

confidence: 70%

A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

et al. 2015

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Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. Research has shown that dysregulated protease activity may elicit proteolytic cleavage of elafin, thereby impairing the innate immune function of the protein. The aim of this study was to generate variants of elafin (GG- and QQ-elafin) that exhibit increased protease resistance while retaining the biological properties of wild-type (WT) elafin. Similar to WT-elafin, GG- and QQ-elafin variants retained antiprotease activity and susceptibility to transglutaminase-mediated fibronectin cross-linking. However, in contrast to WT-elafin, GG- and QQ-elafin displayed significantly enhanced resistance to degradation when incubated with bronchoalveolar lavage fluid from patients with cystic fibrosis. Intriguingly, both variants, particularly GG-elafin, demonstrated improved lipopolysaccharide (LPS) neutralization properties in vitro. In addition, GG-elafin showed improved anti-inflammatory activity in a mouse model of LPS-induced acute lung inflammation. Inflammatory cell infiltration into the lung was reduced in lungs of mice treated with GG-elafin, predominantly neutrophilic infiltration. A reduction in MCP-1 levels in GG-elafin treated mice compared to the LPS alone treatment group was also demonstrated. GG-elafin showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases characterized by a protease burden.

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Section: Discussionsupporting

confidence: 70%

A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

et al. 2015

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“…Likewise, Perkins et al (39) suggested that endostatin levels might be used as a measure of alveolar capillary damage and support a potential pathophysiological role in acute lung injury. We also suggest that impending failure of corneal grafts might be foreshadowed by monitoring endostatin levels.…”

Section: Discussionmentioning

confidence: 99%

Immunological Disruption of Antiangiogenic Signals by Recruited Allospecific T Cells Leads to Corneal Allograft Rejection

Tan

Cruz-Guilloty

Medina-Mendez

et al. 2012

The Journal of Immunology

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Corneal transplantation is the most common solid organ transplantation. The immunologically privileged nature of the cornea results in high success rates. However, T cell-mediated rejection is the most common cause of corneal graft failure. Using antiangiogenesis treatment to prevent corneal neovascularization, which revokes immune privilege, prevents corneal allograft rejection. Endostatin is an antiangiogenic factor that maintains corneal avascularity. In this study, we directly test the role of antiangiogenic and immunological signals in corneal allograft survival, specifically the potential correlation of endostatin production and T cell recruitment. We report that 75% of the corneal allografts of BALB/c mice rejected after postoperative day (POD) 20, whereas all syngeneic grafts survived through POD60. This correlates with endogenous endostatin, which increased and remained high in syngeneic grafts but decreased after POD10 in allografts. Immunostaining demonstrated that early recruitment of allospecific T cells into allografts around POD10 correlated with decreased endostatin production. In Rag−/− mice, both allogeneic and syngeneic corneal grafts survived; endostatin remained high throughout. However, after T cell transfer, the allografts eventually rejected, and endostatin decreased. Furthermore, exogenous endostatin treatment delayed allograft rejection and promoted survival secondary to angiogenesis inhibition. Our results suggest that endostatin plays an important role in corneal allograft survival by inhibiting neovascularization and that early recruitment of allospecific T cells into the grafts promotes destruction of endostatin-producing cells, resulting in corneal neovascularization, massive infiltration of effector T cells, and ultimately graft rejection. Therefore, combined antiangiogenesis and immune suppression will be more effective in maintaining corneal allograft survival.

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“…Due to their critical role in promoting tumor growth and metastasis, anti-tumor angiogenesis has become an important cancer therapy target ( Li and Cozzi, 2010 ; Hanahan and Weinberg, 2011 ). Endostatin is a 20 kDa carboxy-terminal fragment of collagen XVIII and has a strong effect on tumor growth inhibition ( Perkins et al, 2009 ). Several researches showed that endostatin exhibited broad-spectrum antitumor activity in many cancers, such as liver cancer, breast cancer, gastric cancer, and CRC ( Ma et al, 2004 ; Chen et al, 2013 ; Li et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Recombinant Bifidobacterium longum Carrying Endostatin Protein Alleviates Dextran Sodium Sulfate-Induced Colitis and Colon Cancer in Rats

Cui

Yao

et al. 2022

Front. Microbiol.

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Bifidobacterium has been widely administrated orally as probiotics to prevent pathogen colonization and modulate the gut microbiome balance. Endostatin is an endogenous inhibitor of angiogenesis and has been shown to inhibit tumor growth, invasion, and metastasis. At present, the combination of endostatin and chemotherapeutic drugs has been regarded as a promising antitumor treatment strategy. In this study, we selected a safe strain of Bifidobacterium longum as a delivery system to transport endostatin to the gastrointestinal tract and explored their combined effect on inflammatory bowel disease (IBD) and colitis-associated cancer. The results indicated that B. longum-Endo relieved dextran sulfate sodium-induced body weight loss, diarrhea, colon shortening, and epithelium damage. Long-term oral administration of B. longum-Endo significantly decreased tumor formation rate, tumor number, and tumor size. Moreover, the effect of B. longum-Endo on gut microbiota dysbiosis was also confirmed by 16S rRNA sequencing analysis. The levels of potentially beneficial bacteria, such as Lactobacillus, Bifidobacterium, Allobaculum, and Parabateroides, were increased in the B. longum-Endo group compared to the model and B. longum groups. Meanwhile, levels of potentially pathogenic bacteria including Desulfovibrio, Helicobacter, and Enterorhabdus were decreased. Taken together, these results suggested that oral administration of recombinant B. longum-Endo strain may be a promising therapeutic strategy for IBD and colitis-associated cancer.

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Type XVIII collagen degradation products in acute lung injury

Cited by 12 publications

References 33 publications

A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

Immunological Disruption of Antiangiogenic Signals by Recruited Allospecific T Cells Leads to Corneal Allograft Rejection

Recombinant Bifidobacterium longum Carrying Endostatin Protein Alleviates Dextran Sodium Sulfate-Induced Colitis and Colon Cancer in Rats

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