Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with β-tryptase monomers

Strik, Merel C.M.; Wolbink, Angela M.; Wouters, Dorine; Bladergroen, Bellinda A.; Verlaan, Angelique R.; Houdt, Inge S. van; Hijlkema, Sanne; Hack, C. E.; Kummer, J. Alain

doi:10.1182/blood-2003-08-2981

Cited by 41 publications

(40 citation statements)

References 41 publications

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“…We observed leptin expression in the MCs within the lesion. In all tumour MCs, the staining for both MC markers was less pronounced compared to the expression level of MCs in the normal skin, which is in congruence with previous literature (Strik et al 2004). Leptin receptor expression was studied in Wve patients with skin mastocytosis to evaluate if leptin receptors are also present on neoplastic MCs.…”

Section: Discussionsupporting

confidence: 63%

Human mast cells express leptin and leptin receptors

Taildeman

Pérez-Novo

Rottiers

et al. 2009

Histochem Cell Biol

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Mast cells are immune cells that produce and secrete a variety of mediators and cytokines that influence various inflammatory and immune processes. Leptin is a cytokine regulating metabolic, endocrine as well as immune functions via the leptin receptor which is expressed by many immune cells. However, there are no data about leptin receptor expression in mast cells. Immunohistochemical and immunofluorescent double stainings showed the expression of leptin and leptin receptors in mast cells in human skin and several parts of the respiratory, gastrointestinal and urogenital tract. Leptin was expressed in mast cells expressing the classification marker chymase, whereas a variable expression was observed in tryptase positive mast cells. For leptin receptors, the expression pattern was tissue dependent and not related to tryptase or chymase expression. Our results demonstrate the expression of leptin and leptin receptors on mast cells, suggesting paracrine and/or autocrine immunomodulatory effects of leptin on mast cells.

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Section: Discussionsupporting

confidence: 63%

Human mast cells express leptin and leptin receptors

Taildeman

Pérez-Novo

Rottiers

et al. 2009

Histochem Cell Biol

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“…SERPINB6 is also known as proteinase inhibitor 6 or placental thrombin inhibitor, and may contribute to the secondary pathology of myelomeningocele for its role in anti-viral, anti-apoptotic effects, and fibrinolysis. 34–36 SERPINB6 also endogeneously inhibits neuropsin, which modifies synaptic plasticity and long-term potentiation. 37,38 Many other genes with previously unknown associations with myelomeningocele or spinal development were up- or down-regulated, but none to the extent of SERPINB6 (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele

Tarui

Kim

Flake

et al. 2017

American Journal of Obstetrics and Gynecology

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Background Cell-free (cf) RNA in amniotic fluid supernatant (AFS) reflects developmental changes in gene expression in the living fetus, including genes specific to the central nervous system (CNS). Although it has been previously shown that CNS-specific transcripts are present in AFS, it is not known whether changes in the AFS transcriptome reflect the specific pathophysiology of fetal CNS disorders. In myelomeningocele, there is open communication between the CNS and amniotic fluid. Objectives To identify molecular pathophysiologic changes and novel disease mechanisms specific to myelomeningocele by analyzing AFS cfRNA in fetuses with open myelomeningocele. Study Design AFS was collected from 10 pregnant women at the time of the open myelomeningocele repair in the second trimester (24.5+/−1.0 wks) and 10 archived AFS from sex and gestational age-matched euploid fetuses without myelomeningocele were used as controls (20.9+/−0.9 wks). Differentially regulated gene expression patterns were analyzed using Human Genome U133 Plus 2.0 arrays. Results Fetuses with myelomeningocele had 284 differentially-regulated genes (176 up- & 108 down-regulated) in AFS. Known genes associated with myelomeningocele (PRICKLE2, GLI3, RAB23, HES1, FOLR1) and novel dysregulated genes were identified in association with neurodevelopment and neuronal regeneration (up-regulated, GAP43 and ZEB1) or axonal growth and guidance (down-regulated, ACAP1). Pathway analysis demonstrated a significant contribution of inflammation to pathology and a broad influence of Wnt signaling pathways (Wnt1, Wnt5A, ITPR1). Conclusion(s) Transcriptomic analyses of living fetuses with myelomeningocele using AFS cfRNA demonstrated differential regulation of specific genes and molecular pathways relevant to this CNS disorder, resulting in a new understanding of pathophysiological changes. The data also suggested the importance of pathways involving secondary pathology, such as inflammation, in myelomeningocele. These newly identified pathways may lead to hypotheses that can test novel therapeutic targets as adjuncts to fetal surgical repair.

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“…Recent studies have shown that monomers formed under certain conditions have some distinct enzymatic activity [23][24][25] and appear to be responsible for the cleavage of some large proteins [23], but in contrast to the tetramer are sensitive to endogenous inhibitors, e.g. antithrombin III, serpin B6, and -2-macroglobulin [24,26].…”

Section: Tryptasementioning

confidence: 98%

Mast Cell Tryptase β as a Target in Allergic Inflammation: An Evolving Story

Sommerhoff¹,

Schaschke²

2007

CPD

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Tryptases comprise a group of trypsin-like serine proteases that are highly and selectively expressed in mast cells and to a lesser extent in basophils. Among them interest has been focused on tryptase beta, primarily because it was the first tryptase identified and because it is the predominant protease and protein component of mast cells. Subsequent studies have provided convincing evidence that tryptase beta is not only a clinically useful marker of mast cells and their activation but that it contributes to the pathogenesis of allergic inflammatory disorders, most notably asthma. The pathogenetic relevance together with the apparent lack of overt physiological functions has caused considerable interest in beta-tryptase as a potential therapeutic target. Meanwhile diverse tryptase inhibitors have been synthesized whose design in part was fostered by the structural analysis of the enzymatically active beta tryptase tetramer. Various compounds have been studied both in animal models and in man, providing proof of principle that tryptase inhibitors have therapeutic potential in asthma. Here we review the rationale to develop tryptase inhibitors and the approaches pursued, and also try to pinpoint some of the problems that hamper the development of clinically applicable drugs.

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Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with β-tryptase monomers

Cited by 41 publications

References 41 publications

Human mast cells express leptin and leptin receptors

Human mast cells express leptin and leptin receptors

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele

Mast Cell Tryptase β as a Target in Allergic Inflammation: An Evolving Story

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Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with β-tryptase monomers

Cited by 41 publications

References 41 publications

Human mast cells express leptin and leptin receptors

Human mast cells express leptin and leptin receptors

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele

Mast Cell Tryptase &#946; as a Target in Allergic Inflammation: An Evolving Story

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Mast Cell Tryptase β as a Target in Allergic Inflammation: An Evolving Story