Serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibits the rat embryo implantation in vivo and interferes with cell adhesion in vitro

Contraception ◽  
2011 ◽  
Vol 84 (6) ◽  
pp. 642-648 ◽  
Author(s):  
Ya-hong Jiang ◽  
Yan Shi ◽  
Ya-ping He ◽  
Jing Du ◽  
Run-sheng Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Embryo Implantation ◽  
Serine Protease Inhibitor ◽  
Rat Embryo

scholarly journals Mesenchymal stem cells express serine protease inhibitor to evade the host immune response

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1176-1183 ◽  
Author(s):  
Najib El Haddad ◽  
Dean Heathcote ◽  
Robert Moore ◽  
Sunmi Yang ◽  
Jamil Azzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Cytotoxic T Cell ◽  
Wild Type

Abstract Clinical trials using mesenchymal stem cells (MSCs) have been initiated worldwide. An improved understanding of the mechanisms by which allogeneic MSCs evade host immune responses is paramount to regulating their survival after administration. This study has focused on the novel role of serine protease inhibitor (SPI) in the escape of MSCs from host immunosurveillance through the inhibition of granzyme B (GrB). Our data indicate bone marrow–derived murine MSCs express SPI6 constitutively. MSCs from mice deficient for SPI6 (SPI6−/−) exhibited a 4-fold higher death rate by primed allogeneic cytotoxic T cells than did wild-type MSCs. A GrB inhibitor rescued SPI6−/− MSCs from cytotoxic T-cell killing. Transduction of wild-type MSCs with MigR1-SPI6 also protected MSCs from cytotoxic T cell–mediated death in vitro. In addition, SPI6−/− MSCs displayed a shorter lifespan than wild-type MSCs when injected into an allogeneic host. We conclude that SPI6 protects MSCs from GrB-mediated killing and plays a pivotal role in their survival in vivo. Our data could serve as a basis for future SPI-based strategies to regulate the survival and function of MSCs after administration and to enhance the efficacy of MSC-based therapy for diseases.

PIVL, a snake venom Kunitz-type serine protease inhibitor, inhibits in vitro and in vivo angiogenesis

2014 ◽  
Vol 95 ◽  
pp. 149-156 ◽  
Author(s):  
Maram Morjen ◽  
Stéphane Honoré ◽  
Amine Bazaa ◽  
Zaineb Abdelkafi-Koubaa ◽  
Ameneallah Ellafi ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Snake Venom ◽  
Serine Protease Inhibitor ◽  
Kunitz Type

In vivo contribution of serine proteases to the proteolytic activation of γENaC in aldosterone-infused rats

2012 ◽  
Vol 303 (7) ◽  
pp. F939-F943 ◽  
Author(s):  
Kohei Uchimura ◽  
Yutaka Kakizoe ◽  
Tomoaki Onoue ◽  
Manabu Hayata ◽  
Jun Morinaga ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Proteases ◽  
Serine Protease Inhibitor ◽  
Proteolytic Activation ◽  
New Strategy ◽  
Salt Sensitive Hypertension ◽  
Primary Cleavage

Aldosterone plays an important role in the regulation of blood pressure by modulating the activity of the epithelial sodium channel (ENaC) that consists of α-, β-, and γ-subunits. Aldosterone induces a molecular weight shift of γENaC from 85 to 70 kDa that is necessary for the channel activation. In vitro experiments demonstrated that a dual cleavage mechanism is responsible for this shift. It has been postulated that furin executes the primary cleavage in the Golgi and that the second cleavage is provided by other serine proteases such as prostasin or plasmin at the plasma membrane. However, the in vivo contribution of serine proteases to this cleavage remains unclear. To address this issue, we administered the synthetic serine protease inhibitor camostat mesilate (CM) to aldosterone-infused rats. CM decreased the abundance of the 70-kDa form of ENaC and led to a new 75-kDa form with a concomitant increase in the urinary Na-to-K ratio. Because CM inhibits the protease activity of serine proteases such as prostasin and plasmin, but not furin, our findings strongly indicate that CM inhibited the second cleavage of γENaC and subsequently suppressed ENaC activity. The results of our current studies also suggest the possibility that the synthetic serine protease inhibitor CM might represent a new strategy for the treatment of salt-sensitive hypertension in humans.

scholarly journals Serine protease inhibitor disrupts sperm motility leading to reduced fertility in female mice†

2020 ◽  
Vol 103 (2) ◽  
pp. 400-410 ◽  
Author(s):  
Brooke E Barton ◽  
Jenna K Rock ◽  
Anna M Willie ◽  
Emily A Harris ◽  
Ryan M Finnerty ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Cell Viability ◽  
Serine Protease ◽  
Sperm Motility ◽  
Reproductive Tract ◽  
Serine Protease Inhibitor ◽  
Female Reproductive Tract ◽  
Female Mice

Abstract Inhibition of the sperm transport process in the female reproductive tract could lead to infertility. We previously showed that a pan-serine protease inhibitor, 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), blocked semen liquefaction in vivo and resulted in a drastic decrease in the number of sperm in the oviduct of female mice. In this study, we used a mouse model to test the efficacy of AEBSF as a reversible contraceptive, a sperm motility inhibitor, and a spermicide. Additionally, this study evaluated the toxicity of AEBSF on mouse vaginal tissues in vivo and human endocervical cells in vitro. We found that female mice treated with AEBSF had significantly less pups born per litter as well as fertilization rates in vivo compared to the vehicle control. We then showed that AEBSF reduced sperm motility and fertilization capability in vitro in a dose-dependent manner. Furthermore, AEBSF also exhibited spermicidal effects. Lastly, AEBSF treatment in female mice for 10 min or 3 consecutive days did not alter vaginal cell viability in vivo, similar to that of the vehicle and non-treated controls. However, AEBSF decreased cell viability of human ectocervical (ECT) cell line in vitro, suggesting that cells in the lower reproductive tract in mice and humans responded differently to AEBSF. In summary, our study showed that AEBSF can be used as a prototype compound for the further development of novel non-hormonal contraceptives for women by targeting sperm transport in the female reproductive tract.

scholarly journals Transcription of the Rat Serine Protease Inhibitor 2.1 Gene in Vivo: Correlation with GAGA Box Promoter Occupancy and Mechanism of Cytokine-Mediated Down-Regulation

1998 ◽  
Vol 12 (3) ◽  
pp. 391-404 ◽  
Author(s):  
Anne Emmanuelle Simar-Blanchet ◽  
Catherine Legraverend ◽  
Jean Paul Thissen ◽  
Alphonse Le Cam
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Gene Transcription ◽  
Binding Proteins ◽  
Serine Protease Inhibitor ◽  
Dnase I ◽  
Down Regulation ◽  
Response Element

Abstract Two GH-response elements (GHREs) and a single glucocorticoid (GC)-response element were found to regulate activity of the rat serine protease inhibitor 2.1 gene (spi 2.1) promoter in vitro. To assess the physiological relevance of these observations, we have investigated the relationship existing between the level of spi 2.1 gene transcription, structural modifications of the chromatin, and in vivo nuclear protein-promoter interactions monitored by genomic footprinting, in control, hypophysectomized, and inflamed rats. We also addressed the mechanism of inflammation-mediated gene down-regulation. We found that a high level of spi 2.1 gene transcription correlates with hypersensitivity of the promoter to deoxyribonuclease I (DNase I) and maximal occupancy of the GAGA box (GHRE-I). The failure of GAGA-box binding proteins (GAGA-BPs) to interact with the GAGA box appears to result from an impairment in GH action due to its absence (i.e. hypophysectomized animals) or to the appearance of a cytokine-mediated GH-resistant state (i.e. inflamed rats) in liver. Unlike the GAGA box, signal transducer and activator of transcription (STAT) factor-binding sites included in the GHRE-II were never found to be protected against DNase I attack but displayed a differential DNase I reactivity depending on the level of gene transcription. Alterations in DNase I reactivity of the GC-response element region suggest that GC receptor-GC complexes may associate, in a transient manner, with the promoter in the actively transcribing control state. Taken together, our studies suggest a mechanism of spi 2.1 gene activation in vivo whereby the GH-dependent chromatin remodeling caused by or concomitant to the recruitment of GAGA-box binding proteins is the first compulsory and presumably predominant step.

scholarly journals Nasal commensal, Staphylococcus epidermidis shapes the mucosal environment to prevent influenza virus invasion through Serpine1 induction

2020 ◽  
Author(s):  
Ara Jo ◽  
Jina Won ◽  
Chan Hee Chil ◽  
Jae Young Choi ◽  
Kang-Mu Lee ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Nasal Mucosa ◽  
Staphylococcus Epidermidis ◽  
Influenza Virus Infection ◽  
Serine Protease Inhibitor ◽  
Cellular Environment

ABSTRACTOur recent study presented evidence that Staphylococcus epidermidis (S. epidermidis) was the most frequently encountered microbiome component in healthy human nasal mucus and that S. epidermidis could induce interferon (IFN)-dependent innate immunity to control acute viral lung infection. The serine protease inhibitor Serpine1 was identified to inhibit influenza A virus (IAV) spread by inhibiting glycoprotein cleavage, and the current study supports an additional mechanism of Serpine1 induction in the nasal mucosa, which can be regulated through S. epidermidis and IFN signaling. The exposure of in vivo mice to human S. epidermidis increased IFN-λ secretion in nasal mucosa and prevented an increase in the burden of IAV in the lung. S. epidermidis-inoculated mice exhibited the significant induction of Serpine1 in vivo in the nasal mucosa, and by targeting airway protease, S. epidermidis-induced Serpine1 inhibited the intracellular invasion of IAV to the nasal epithelium and led to restriction of IAV spreading to the lung. Furthermore, IFN-λ secretion was involved in the regulation of Serpine1 in S. epidermidis-inoculated nasal epithelial cells and in vivo nasal mucosa, and this was biologically relevant for the role of Serpine1 as an interferon-stimulated gene in the upper airway. Together, our findings reveal that human nasal commensal S. epidermidis manipulates the suppression of serine protease in in vivo nasal mucosa through Serpine1 induction and protects the nasal mucosa from IAV invasion through IFN-λ signaling.IMPORTANCEPreviously, we proved that nasal microbiome could enhance IFN-related innate immune responses to protect the respiratory tract against influenza virus infection. The present study shows a great understanding of the intimate association of S. epidermidis-regulated IFN-lambda induction and serine protease inhibitor in nasal mucosa. Our data demonstrate that S. epidermidis-regulated Serpine1 suppresses the invasion of influenza virus through suppression of airway serine protease at the level of nasal mucosa and impedes IAV spread to the respiratory tract. Thus, human nasal commensal S. epidermidis represents a therapeutic potential for treating respiratory viral infections via the change of cellular environment in respiratory tract.

scholarly journals Targeted Disruption of Toxoplasma gondii Serine Protease Inhibitor 1 Increases Bradyzoite Cyst FormationIn Vitroand Parasite Tissue Burden in Mice

2011 ◽  
Vol 80 (3) ◽  
pp. 1156-1165 ◽  
Author(s):  
Viviana Pszenny ◽  
Paul H. Davis ◽  
Xing W. Zhou ◽  
Christopher A. Hunter ◽  
Vern B. Carruthers ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Protease Inhibitor ◽  
Host Cell ◽  
Serine Protease ◽  
Parasitophorous Vacuole ◽  
Parasite Burden ◽  
Serine Protease Inhibitor ◽  
Genomic Locus ◽  
Content Type

As an intracellular protozoan parasite,Toxoplasma gondiiis likely to exploit proteases for host cell invasion, acquisition of nutrients, avoidance of host protective responses, escape from the parasitophorous vacuole, differentiation, and other activities.T. gondiiserine protease inhibitor 1 (TgPI1) is the most abundantly expressed protease inhibitor in parasite tachyzoites. We show here that alternative splicing produces twoTgPI1 isoforms, both of which are secreted via dense granules into the parasitophorous vacuole shortly after invasion, become progressively more abundant over the course of the infectious cycle, and can be detected in the infected host cell cytoplasm. To investigateTgPI1 function, the endogenous genomic locus was disrupted in the RH strain background. ΔTgPI1 parasites replicate normally as tachyzoites but exhibit increased bradyzoite gene transcription and labeling of vacuoles withDolichos bifloruslectin under conditions promotingin vitrodifferentiation. The differentiation phenotype can be partially complemented by eitherTgPI1 isoform. Mice infected with the ΔTgPI1 mutant display ∼3-fold-increased parasite burden in the spleen and liver, and thisin vivophenotype is also complemented by eitherTgPI1 isoform. These results demonstrate thatTgPI1 influences both parasite virulence and bradyzoite differentiation, presumably by inhibiting parasite and/or host serine proteases.

scholarly journals Serine Protease Inhibitor Kunitz-Type 2 Is Downregulated in Myelodysplastic Syndromes and Modulates Cell–Cell Adhesion

2014 ◽  
Vol 23 (10) ◽  
pp. 1109-1120 ◽  
Author(s):  
Fernanda Marconi Roversi ◽  
Matheus Rodrigues Lopes ◽  
João Agostinho Machado-Neto ◽  
Ana Leda F. Longhini ◽  
Adriana da Silva Santos Duarte ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Myelodysplastic Syndromes ◽  
Serine Protease Inhibitor ◽  
Kunitz Type ◽  
Cell Cell

In Vitro Dose Ranging Studies for Serine Protease Inhibitor, MK-4519, Against a Hepatitis C Virus (HCV) Replicon using the Bellocell System

2010 ◽  
Vol 86 (1) ◽  
pp. A30
Author(s):  
Ashley N. Brown ◽  
D.V. Singer ◽  
J.J. McSharry ◽  
R.J.O. Barnard ◽  
D.J. Hazuda ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Dose Ranging

scholarly journals Structural modeling and thermostability of a serine protease inhibitor belonging to the Kunitz family from the tick Rhipicephalus microplus

2020 ◽  
Author(s):  
Lívia de Moraes Bomediano Camillo ◽  
Graziele Cristina Ferreira ◽  
Adriana Feliciano Alves Duran ◽  
Flavia Ribeiro Santos da Silva ◽  
Wanius Garcia ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Disulfide Bonds ◽  
Tertiary Structure ◽  
Dissociation Constants ◽  
Serine Protease Inhibitor ◽  
Rhipicephalus Microplus ◽  
Human Neutrophil Elastase ◽  
Structure Stabilization

ABSTRACTrBmTI-A is a recombinant serine protease inhibitor that belongs to the Kunitz-BPTI family and that was cloned from Rhipicephalus microplus tick. rBmTI-A has inhibitory activities on bovine trypsin, human plasma kallikrein, human neutrophil elastase and plasmin with dissociation constants in nM range. It is characterized by two inhibitory domains and each domain presents six cysteines that form three disulfide bonds, which contribute to the high stability of its structure. Previous studies suggest that serine protease inhibitor rBmTI-A has a protective potential against pulmonary emphysema in mice and anti-inflammatory potential, besides rBmTI-A presented a potent inhibitory activity against in vitro vessel formation. In this study, the tertiary structure of BmTI-A was modeled based on the structure of its Sabellastarte magnifica homologue. The structure stabilization was evaluated by molecular dynamics analysis. Circular dichroism data corroborated the secondary structure found by the homology modeling. Thermostability analysis confirmed the thermostability and the relation between the effects of the temperature in the inhibitor activity. The loss of activity observed was gradual, and, after 60 minutes of incubation at 90°C the inhibitor lost it completely.

Sign in / Sign up

Export Citation Format

Share Document