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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Regulatory role of Semaphorin3E on human neutrophils migration

Saati, Abeer Abdullah 17 January 2013 (has links)
Semaphorin3E (Sema3E) is a secreted protein that was originally implicated in the development of the nervous system. However, its role in processes other than neuronal guidance is not fully understood. Sema3E interacts with the receptor PlexinD1 with high affinity. Furthermore, differential expression of PlexinD1 with neuropilin-1 (Nrp1) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) determines pro-migratory or anti-migratory property of Sema3E. Recent studies demonstrated that semaphorins exhibit an inhibitory effect in most of inflammatory diseases. Among all inflammatory cells, neutrophils are an indispensable component of innate immunity and they are the foremost cells migrating to the site of inflammation. Substantial evidence indicated that the number of neutrophils is elevated in many inflammatory diseases. The aim of this study is to determine the expression pattern of Sema3E and its receptors, PlexinD1, Nrp1 and VEGFR2 in human neutrophils and to investigate the role of Sema3E on neutrophils’ migration. Here we found that isolated human neutrophils, from peripheral blood of healthy volunteers, constitutively express Sema3E and its receptors PlexinD1 and VEGFR2 at both protein and mRNA level; however, Nrp1 expression was not detected in these cells. Additionally, Sema3E display a potent ability to inhibit CXCL8/IL-8 induced neutrophils migration as determined by transwell in vitro system and microfluidic device coupled to real-time microscopy. Our data showed that Sema3E modulates the migration of neutrophils induced by the most potent chemoattractant stimuli, CXCL8/IL-8, suggesting an important regulatory role of this pathway in inflammatory diseases associated with neutrophilia.
2

Regulatory role of Semaphorin3E on human neutrophils migration

Saati, Abeer Abdullah 17 January 2013 (has links)
Semaphorin3E (Sema3E) is a secreted protein that was originally implicated in the development of the nervous system. However, its role in processes other than neuronal guidance is not fully understood. Sema3E interacts with the receptor PlexinD1 with high affinity. Furthermore, differential expression of PlexinD1 with neuropilin-1 (Nrp1) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) determines pro-migratory or anti-migratory property of Sema3E. Recent studies demonstrated that semaphorins exhibit an inhibitory effect in most of inflammatory diseases. Among all inflammatory cells, neutrophils are an indispensable component of innate immunity and they are the foremost cells migrating to the site of inflammation. Substantial evidence indicated that the number of neutrophils is elevated in many inflammatory diseases. The aim of this study is to determine the expression pattern of Sema3E and its receptors, PlexinD1, Nrp1 and VEGFR2 in human neutrophils and to investigate the role of Sema3E on neutrophils’ migration. Here we found that isolated human neutrophils, from peripheral blood of healthy volunteers, constitutively express Sema3E and its receptors PlexinD1 and VEGFR2 at both protein and mRNA level; however, Nrp1 expression was not detected in these cells. Additionally, Sema3E display a potent ability to inhibit CXCL8/IL-8 induced neutrophils migration as determined by transwell in vitro system and microfluidic device coupled to real-time microscopy. Our data showed that Sema3E modulates the migration of neutrophils induced by the most potent chemoattractant stimuli, CXCL8/IL-8, suggesting an important regulatory role of this pathway in inflammatory diseases associated with neutrophilia.
3

SEMA3E REGULATES RESIDENT MACROPHAGES RESPONSE IN LIPOPOLYSACCHARIDE-INDUCED SEPSIS

Mohammed, Ashfaque 01 September 2016 (has links)
Sepsis is an overwhelming systemic inflammatory response to microbial infections. Macrophages are the key innate immune cells that provide the first line of defence against systemic infections during sepsis. Macrophages perform multiple functions during infections such as triggering inflammation, phagocytosis of microbes, and resolution of inflammation. So far, various molecules have been shown to be involved in the regulation of macrophages in inflammatory conditions. However, recently published studies suggest that Semaphorin3E (Sema3E) plays a pivotal role in the immune function of macrophages. The exact role of Sema3E associated with macrophages function in lipopolysaccharide (LPS) induced endotoxemia is unknown. To directly address the involvement of Sema3E in macrophages, we have used Sema3e gene deletion approaches in in vivo and cell-based setups. We found that Sema3e-/- mice displayed initial transient protection from LPS-induced hypothermia. Sema3e-/- mice showed lower inducible nitric oxide synthase (iNOS) expression in peritoneal macrophages without altering the integrity of TLR-4 after LPS injection. Sema3e-/- mice exhibit a lower level of tumour necrosis factor (TNF) and interleukin-6 (IL-6) in peritoneal lavage and serum as compared to wild type (WT) littermates. Bone marrow derived macrophages (BMDMs) from Sema3e-/- mice expressed low levels of pro-inflammatory cytokines and also exhibited significantly down-regulated phosphorylation of STAT3, ERK1/2, and NF-κB, upon LPS exposure. Overall, the current study provides direct evidence that the lack of Sema3E, makes macrophages to become less responsive to LPS by disturbing LPSIII initiated signaling transduction. These findings suggest that the inhibition of Sema3E might be a novel strategy to treat conditions triggered by the excessive production of inflammatory cytokines. / October 2016
4

Effect of semaphorin 3E on airway smooth muscle cell in chronic obstructive pulmonary disease (COPD)

Alsubait, Duaa 08 April 2015 (has links)
Introduction: Our objective is to investigate whether Semaphorin 3E (sema3E) regulates human airway smooth muscle cell (HASMC) proliferation in chronic obstructive pulmonary disease (COPD). Methods: HASMCs and tissues were isolated from COPD patients. Sema3E and plexinD1 expressions were studied using Q-PCR, FACS, IHC and immunoblotting. Cell proliferation was evaluated using FACS. Results: HASM cells from COPD patients express p61kDa-Sema3E isoform and plexinD1 at mRNA and protein level. Lung tissue from COPD and healthy subjects display Sema3E immunoreactivity. Treatment with Sema3E inhibits HASM cell proliferation mediated by PDGF in healthy, but not in COPD. HASM cells from COPD patient display surface expression of Sema3E. Conclusion: The absence of effect of recombinant Sema3E in COPD is due the constitutive expression and release of p61kDa-Sema3E isoform, which may account for airway remodeling in COPD. / May 2015
5

Développement d’une thérapie ciblée anticancéreuse dirigée contre le couple SEMA3E/PLXND1 / Development of a targeted ant-cancer therapy against Sema3E/PlxnD1

Favrot, Clémentine 23 June 2017 (has links)
Les protéines Sémaphorines et leurs récepteurs Plexines jouent un rôle primordial dans le réseau de signalisation cellulaire. Initialement découvertes pour leur rôle dans le guidage axonal, il fut rapidement mis en lumière qu'elles étaient également impliquées dans le développement du système cardiovasculaire, dans la tumorigénèse et le fonctionnement du système immunitaire, démontrant les multiples facettes de ces protéines. Parmi ces couples de ligands et de récepteurs, la Sémaphorine 3E et son récepteur Plexine D1 représentent des cibles d'intérêt pour les thérapies anti-cancéreuses. La Sémaphorine 3E est surexprimée dans de nombreux cancers et son expression est corrélée à la dissémination métastatique et à la progression tumorale. Ces travaux de thèse ont donc consisté en la caractérisation de ce couple en temps que nouvelle cible anti-tumorale et le développement d'une thérapie ciblée qui a montré des effets prometteurs dans les études pré-cliniques en combinaison avec d'autres thérapies innovantes / The Semaphorin proteins and their receptors Plexins play a primordial role in the cell signaling network. Initially discovered for their role in axonal guidance, it was soon identified that they also are implied in cardiovascular system development, tumorigenesis and immune system functioning, demonstrating the multiple facets of these proteins. Among these pairs of ligands and receptors, Semaphorin 3E and its receptor Plexin D1 represent targets of interest for anticancer therapies. Semaphorin 3E is overexpressed in many cancers and its expression is correlated with metastatic dissemination and tumor progression. This work consisted in characterizing Sema3E/PlxnD1 as new anti-tumor target and developing a targeted therapy. Combination between this therapy and other innovative drugs provided promising results in preclinical studies

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