The role of secretory leucoprotease inhibitor in the resolution of inflammatory responses

Chronic lung disease is one of the most common causes of death and disability worldwide. This group of diseases is characterized by a protease burden, an infective process and a dominant pro-inflammatory profile. While SLPI (secretory leucoprotease inhibitor) was initially identified as a serine protease inhibitor, it has since been shown that SLPI possesses other properties distinct from those associated with its antiprotease capabilities that play an important role in protecting the host from infection and injury. In the course of this review, we will highlight the findings from a range of studies that illustrate the multiple functions of SLPI and its role in the resolution of the immune response.

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Carbohydrate-controlled serine protease inhibitor (serpin) production in Bifidobacterium longum subsp. longum

Scientific Reports ◽

10.1038/s41598-021-86740-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

S. Duboux ◽

M. Golliard ◽

J. A. Muller ◽

G. Bergonzelli ◽

C. J. Bolten ◽

...

Keyword(s):

Protease Inhibitor ◽

Serine Protease ◽

Serine Proteases ◽

Intestinal Tract ◽

Defense Mechanism ◽

Inflammatory Diseases ◽

Bifidobacterium Longum ◽

Serine Protease Inhibitor ◽

Innate Defense

AbstractThe Serine Protease Inhibitor (serpin) protein has been suggested to play a key role in the interaction of bifidobacteria with the host. By inhibiting intestinal serine proteases, it might allow bifidobacteria to reside in specific gut niches. In inflammatory diseases where serine proteases contribute to the innate defense mechanism of the host, serpin may dampen the damaging effects of inflammation. In view of the beneficial roles of this protein, it is important to understand how its production is regulated. Here we demonstrate that Bifidobacterium longum NCC 2705 serpin production is tightly regulated by carbohydrates. Galactose and fructose increase the production of this protein while glucose prevents it, suggesting the involvement of catabolite repression. We identified that di- and oligosaccharides containing galactose (GOS) and fructose (FOS) moieties, including the human milk oligosaccharide Lacto-N-tetraose (LNT), are able to activate serpin production. Moreover, we show that the carbohydrate mediated regulation is conserved within B. longum subsp. longum strains but not in other bifidobacterial taxons harboring the serpin coding gene, highlighting that the serpin regulation circuits are not only species- but also subspecies- specific. Our work demonstrates that environmental conditions can modulate expression of an important effector molecule of B. longum, having potential important implications for probiotic manufacturing and supporting the postulated role of serpin in the ability of bifidobacteria to colonize the intestinal tract.

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Advances in the understanding of trauma-induced coagulopathy

Blood ◽

10.1182/blood-2016-01-636423 ◽

2016 ◽

Vol 128 (8) ◽

pp. 1043-1049 ◽

Cited By ~ 120

Author(s):

Ronald Chang ◽

Jessica C. Cardenas ◽

Charles E. Wade ◽

John B. Holcomb

Keyword(s):

Animal Studies ◽

Causes Of Death ◽

Endothelial Activation ◽

The United States ◽

Trauma Patients ◽

Platelet Dysfunction ◽

Intracranial Injury ◽

Trauma Induced Coagulopathy ◽

Common Causes

Abstract Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory-based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be “normal” after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge.

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A Model to Evaluate Toxic Factors Influencing Islets during Collagenase Digestion: The Role of Serine Protease Inhibitor in the Protection of Islets

Cell Transplantation ◽

10.3727/096368911x605385 ◽

2012 ◽

Vol 21 (2-3) ◽

pp. 473-482 ◽

Cited By ~ 8

Author(s):

Manabu Tsukada ◽

Takuro Saito ◽

Kazuya Ise ◽

Akira Kenjo ◽

Takashi Kimura ◽

...

Keyword(s):

Protease Inhibitor ◽

Serine Protease ◽

Serine Protease Inhibitor ◽

Factors Influencing ◽

Collagenase Digestion ◽

Toxic Factors

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The Role of Mast Cells in Stroke

Cells ◽

10.3390/cells8050437 ◽

2019 ◽

Vol 8 (5) ◽

pp. 437 ◽

Cited By ~ 8

Author(s):

Edoardo Parrella ◽

Vanessa Porrini ◽

Marina Benarese ◽

Marina Pizzi

Keyword(s):

Central Nervous System ◽

Immune Response ◽

Nervous System ◽

Mast Cells ◽

Brain Edema ◽

Hemorrhagic Stroke ◽

Inflammatory Responses ◽

Adult Brain ◽

The Central Nervous System

Mast cells (MCs) are densely granulated perivascular resident cells of hematopoietic origin. Through the release of preformed mediators stored in their granules and newly synthesized molecules, they are able to initiate, modulate, and prolong the immune response upon activation. Their presence in the central nervous system (CNS) has been documented for more than a century. Over the years, MCs have been associated with various neuroinflammatory conditions of CNS, including stroke. They can exacerbate CNS damage in models of ischemic and hemorrhagic stroke by amplifying the inflammatory responses and promoting brain–blood barrier disruption, brain edema, extravasation, and hemorrhage. Here, we review the role of these peculiar cells in the pathophysiology of stroke, in both immature and adult brain. Further, we discuss the role of MCs as potential targets for the treatment of stroke and the compounds potentially active as MCs modulators.

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