Inflammation-Mediating Proteases: Structure, Function in (Patho) Physiology and Inhibition

2014 ◽  
Vol 21 (12) ◽  
pp. 1209-1229
Author(s):  
Mateja Mancek-Keber

Proteases regulating inflammation are versatile enzymes, usually extracellular matrix degrading enzymes that are involved in wound healing, angiogenesis, coagulation, development, apoptosis and other physiological processes. Their dysregulation and increased expression during inflammation can have devastating consequences, promoting etiology of vascular diseases, inflammatory arthritis, cancer, and allograft rejection. In this review several proteases (ADAMTS, granzymes, plasmin, and kallikreins) with different mechanisms and substrates are described in addition to their physiological roles and contribution to inflammation and inflammatory diseases. Inhibition of proteases may therefore represent an attractive strategy for treatment and herein we describe physiological and engineered inhibitors.

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0245708
Author(s):  
Eun Seob Lim ◽  
Seung-Youb Baek ◽  
Taeyoung Oh ◽  
Minseon Koo ◽  
Joo Young Lee ◽  
...  

Bacillus cereus is a foodborne pathogen and can form biofilms on food contact surfaces, which causes food hygiene problems. While it is necessary to understand strain-dependent variation to effectively control these biofilms, strain-to-strain variation in the structure of B. cereus biofilms is poorly understood. In this study, B. cereus strains from tatsoi (BC4, BC10, and BC72) and the ATCC 10987 reference strain were incubated at 30°C to form biofilms in the presence of the extracellular matrix-degrading enzymes DNase I, proteinase K, dispase II, cellulase, amyloglucosidase, and α-amylase to assess the susceptibility to these enzymes. The four strains exhibited four different patterns in terms of biofilm susceptibility to the enzymes as well as morphology of surface-attached biofilms or suspended cell aggregates. DNase I inhibited the biofilm formation of strains ATCC 10987 and BC4 but not of strains BC10 and BC72. This result suggests that some strains may not have extracellular DNA, or their extracellular DNA may be protected in their biofilms. In addition, the strains exhibited different patterns of susceptibility to protein- and carbohydrate-degrading enzymes. While other strains were resistant, strains ATCC 10987 and BC4 were susceptible to cellulase, suggesting that cellulose or its similar polysaccharides may exist and play an essential role in their biofilm formation. Our compositional and imaging analyses of strains ATCC 10987 and BC4 suggested that the physicochemical properties of their biofilms are distinct, as calculated by the carbohydrate to protein ratio. Taken together, our study suggests that the extracellular matrix of B. cereus biofilms may be highly diverse and provides insight into the diverse mechanisms of biofilm formation among B. cereus strains.


2003 ◽  
Vol 5 (23) ◽  
pp. 1-39 ◽  
Author(s):  
Marc A. Lafleur ◽  
Madeleine M. Handsley ◽  
Dylan R. Edwards

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is an integral part of physiological processes such as embryonic development, the female reproductive cycle and wound healing. Angiogenesis is also central to a variety of pathologies including cancer, where it is recognised as being crucial for the growth of solid tumours. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, most notably MMP-2 and -9 and membrane-type-1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, liberation of angiogenic factors, production of endogenous angiogenic inhibitors, and the unmasking of cryptic biologically relevant sites in ECM components. This review brings together what is currently known about the functions of the MMPs and the closely related adamalysin metalloproteinase (ADAM) family in angiogenesis, and discusses how this information might be useful in manipulation of the angiogenic process, with a view to controlling aberrant neovascularisation.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Young-Ok Son ◽  
Seulki Park ◽  
Ji-Sun Kwak ◽  
Yoonkyung Won ◽  
Wan-Su Choi ◽  
...  

2018 ◽  
Vol 30 (02) ◽  
pp. 1850015
Author(s):  
Bahare Zihayat ◽  
Arash Khodadadi ◽  
Molook Torabi ◽  
Mohammad Mehdipour ◽  
Mohsen Basiri ◽  
...  

Diabetic ulcers (DUs) are a chronic, non-healing diabetes complication that leads to high hospital expenses and, in extreme cases, to amputation. Peripheral vascular diseases, diabetic neuropathy, abnormal cellular and cytokine activity are among the major factors that hinder diabetic wound healing. DUs represent an important challenge in the development of new and efficient wound dressings. The extracellular matrix (ECM) has been effectively used as a scaffold for constructive remodeling of multiple tissues in animal and human. Sheep’s urinary bladder matrix was evaluated for its wound healing activity in streptozotocin-induced diabetic rats using excision model. In this experiment, 48 male Sprague dawley rats weighing 220–250[Formula: see text]g were divided into four equal groups of control, vaseline, diabetics + (10[Formula: see text]mg/wound) and [Formula: see text] (50[Formula: see text]mg/wound). Diabetes was induced by intraperitoneal injection of streptozotocin (45[Formula: see text]mg/kg B.W) solved in 0.05[Formula: see text]M citrate buffer. Seven days after confirming diabetes statue, skin wounds were created on the back of each rat. Rate of wound healing and histological assay using hematoxylin and Eosin staining (H&E) were used for evaluation of the wound healing in different groups. ECM treated animals exhibited significant improvement in both wound area and rate of wound healing when compared to controls ([Formula: see text]). The ECM treated wounds were found to epithelize faster as compared to controls. The sheep’s ECM promotes significant wound healing in male diabetic rats and further studies on this activity in animal models and humans are suggested.


2021 ◽  
Author(s):  
Eun Seob Lim ◽  
Seung-Youb Baek ◽  
Taeyoung Oh ◽  
Minseon Koo ◽  
Joo Young Lee ◽  
...  

Bacillus cereus is a foodborne pathogen and can form biofilms on food contact surfaces, which causes food hygiene problems. While it is necessary to understand strain-dependent variation to effectively control these biofilms, strain-to-strain variation in the structure of B. cereus biofilms is poorly understood. In this study, B. cereus strains from tatsoi and the ATCC 10987 reference strain were incubated at 30? to form biofilms in the presence of the extracellular matrix-degrading enzymes DNase I, proteinase K, dispase II, cellulase, amyloglucosidase, and α-amylase to assess the susceptibility to these enzymes. The four strains exhibited four different patterns in terms of biofilm susceptibility to the enzymes as well as morphology of surface-attached biofilms or suspended cell aggregates. DNase I inhibited the biofilm formation of strains ATCC 10987 and BC4 but not of strains BC10 and BC72. This result suggests that some strains may not have extracellular DNA, or their extracellular DNA may be protected in their biofilms. In addition, the strains exhibited different patterns of susceptibility to protein- and carbohydrate-degrading enzymes. While other strains were resistant, strains ATCC 10987 and BC4 were susceptible to cellulase, suggesting that cellulose or its similar polysaccharides may exist and play an essential role in their biofilm formation. Our compositional analysis of strains ATCC 10987 and BC4 suggested that the physicochemical properties of their biofilms are distinct, as calculated by the carbohydrate to protein ratio. Taken together, our study suggests that the extracellular matrix of B. cereus biofilms may be highly diverse and provides insight into the diverse mechanisms of biofilm formation among B. cereus strains.


Physiology ◽  
1989 ◽  
Vol 4 (1) ◽  
pp. 9-12
Author(s):  
JH Campbell ◽  
GR Campbell

The mechanism by which a change in smooth muscle phenotype is effected in the artery wall during atherogenesis may be via release of extracellular matrix-degrading enzymes, particularly heparanase, from activated macrophages and T lymphocytes.


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