Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(Interleukin1). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of Manchester

1. Zahedi-Nejad, Maryam Sadat. Characterisation of the expression and degradation of the pro-inflammatory cytokine interleukin 1.

Degree: PhD, 2012, University of Manchester

Inflammation plays a crucial role in protecting the host from infection and tissue injury. However, uncontrolled inflammation contributes to the pathogenesis of major auto-inflammatory diseases. Interleukin-1 (IL-1), a pleiotropic pro-inflammatory cytokine, is a pivotal mediator of many of these diseases. The best characterised IL-1 family members, IL-1α and IL-1β, are produced as precursor forms of 31 kDa in size. Both precursors are cleaved and secreted, activating transmembrane IL-1 receptors on IL-1-responsive cells. Many studies that focused on IL-1α have shown that the precursor and processed mature Ct peptide, as well as its N terminus (Nt) form, can elicit a signal. However, with IL-1β, only the processed mature Ct form is known to elicit an inflammatory response and no immunological activity has been attributed to Nt fragments of pro-IL-1β. Therefore, the first objective of this study was to produce recombinant human Nt-IL-1β fragments in bacterial and mammalian expression system to investigate their possible immunomodulatory functions. Recombinant His-tagged N-terminus fragments (10 and 14 kDa) of pro-IL-1β were cloned into the bacterial expression vector pET-22(+) and expressed in E. coli BL21(DE3) followed by purification using three consecutive columns (IMAC, SEC and AEC). Purification analysis of eluted proteins from columns indicated that the recombinant proteins were always co-purified with some other bacterial proteins. The Nt fragments of pro-IL-1β were cloned into the mammalian expression plasmid, pcDNA3.1(+). Expression of these proteins was monitored by transfection of two mammalian cell lines: Human Embryonic Kidney (HEK) 293 cells and monkey kidney cells (COS-7). No protein expression was observed with either construct. These limitations urged us to investigate the expression and degradation of endogenous IL-1 in vitro. Previous studies have shown that the transcription of cytokine genes in response to lipopolysaccharide (LPS) is usually rapid and begins to decline within a few hours after stimulation. The proteasome is the major cellular proteolytic apparatus and controls the turn-over of cellular proteins. We investigated the intracellular stability of IL-1α and IL-1β in LPS-stimulated mouse J774 macrophages and primary mouse bone marrow derived macrophages (BMDMs). Exposure of LPS-stimulated J774 and BMDMs to three different classes of proteasome inhibitors (peptide alhedyde (ALLN), peptide boronate (MG262) and non-peptide inhibitor (β-lactone)) prevented the degradation of intracellular IL-1α and IL-1β in a concentration and time dependent manner. Furthermore, the release of IL-1 into the culture media was not affected by any of these inhibitors in LPS-stimulated J774 cells. However, in LPS-stimulated BMDMs, β-lactone increased the release of both IL-1α and IL-1β and ALLN only increased IL-1α release into culture supernatant compared to control. MG262 had no effect on the release of either. These data suggest that the proteasome plays an important role in controlling the amount of IL-1α and…

Subjects/Keywords: 616.0473; Interleukin1; IL-1a and IL-1ß; Proteasome; Proteasome inhibitors Monocytes; LPS

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Zahedi-Nejad, M. S. (2012). Characterisation of the expression and degradation of the pro-inflammatory cytokine interleukin 1. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-expression-and-degradation-of-the-proinflammatory-cytokine-interleukin-1(ed66d067-bf16-4d1d-ac30-fdb1397d0366).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553479

Chicago Manual of Style (16th Edition):

Zahedi-Nejad, Maryam Sadat. “Characterisation of the expression and degradation of the pro-inflammatory cytokine interleukin 1.” 2012. Doctoral Dissertation, University of Manchester. Accessed October 16, 2019. https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-expression-and-degradation-of-the-proinflammatory-cytokine-interleukin-1(ed66d067-bf16-4d1d-ac30-fdb1397d0366).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553479.

MLA Handbook (7th Edition):

Zahedi-Nejad, Maryam Sadat. “Characterisation of the expression and degradation of the pro-inflammatory cytokine interleukin 1.” 2012. Web. 16 Oct 2019.

Vancouver:

Zahedi-Nejad MS. Characterisation of the expression and degradation of the pro-inflammatory cytokine interleukin 1. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2019 Oct 16]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-expression-and-degradation-of-the-proinflammatory-cytokine-interleukin-1(ed66d067-bf16-4d1d-ac30-fdb1397d0366).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553479.

Council of Science Editors:

Zahedi-Nejad MS. Characterisation of the expression and degradation of the pro-inflammatory cytokine interleukin 1. [Doctoral Dissertation]. University of Manchester; 2012. Available from: https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-expression-and-degradation-of-the-proinflammatory-cytokine-interleukin-1(ed66d067-bf16-4d1d-ac30-fdb1397d0366).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553479


Cleveland State University

2. Narayanan, Padmini. Interleukin 1 Receptor1 signaling in Platelet Inflammatory responses Interleukin-1ß processing and secretion.

Degree: PhD, College of Sciences and Health Professions, 2014, Cleveland State University

Anucleate platelets alter their transcriptome through stimulated splicing of intron and exon containing hnRNA e.g. Interleukin-1ß (IL-1ß), BCL-3. Platelet TLR4 activation upon Lipopolysaccharide (LPS) binding induces accumulation of spliced IL-1ß mRNA and IL-1ß laden microparticle shedding. Interleukin-1 Receptor 1 (IL-1R1) shares downstream signaling molecules with TLR-4, and its presence and possible role in platelet responses is unknown. Here I show that, platelets do express surface IL-R1 and is functional upon binding IL-1ß. Platelet IL-1R1 could recognize endogenous ligands as well observed through the in vivo accumulation of IL-1ß during clot formation in mouse models. Platelets are the primary source of this IL-1ß accumulation, dependent on post transcriptional processing events and translation of platelet IL-1ß mRNA. Proinflammatory IL-1ß is produced as a leader less proprotein and its mode of secretion remains opaque. This study demonstrates that IL-1ß is released in soluble form and also in association with plasma membrane shed microparticles and endo-lysosomal originated exosomes. The distribution of the newly sunthesiszed IL-1ß between these compartments where agonist dependant. Direct visuvalisation of unpermeabilized microparticles with Total Internal Reflection Microscopy and flowcytometry showed IL-1ß surface display. Both microparticles and exosomes contain IL-1R1 and is essential for the IL-1ß display on the particle surface. Blocking IL-1R1 in human platelets with IL-1Ra reduced IL-1ß display on the microparticle surface and complete loss of IL-1R1 in IL-1R1-/- platelet shed microparticles showed no surface IL-1ß. The shed microvesicles contain biologically active IL-1 that activates Nf-¿B driven E-selectin expression in endothelial cells in an IL-1R1 dependent fashion. Efficient IL-1 secretion is bi-parte signaling event, involving the surface receptor ligand stimulation that is closely followed by activation of ATP - induced purinergic P2X7 receptor and NLRP3 inflammasome which facilitate Caspase-1 dependent IL-1ß activation and secretion. Platelets express P2X7 receptors and Pannxein-1 channels, process IL-1ß via NLRP-3 inflammasome complex formation. Inhibition of caspase-1 activity with cell permeable peptide inhibitors, or indirect inhibition of inflammasome assembly through inhibition of P2X7 receptor and Panx-1 activation resulted in decreased IL-1ß laden microparticle release. In summary, this study has identified novel functional platelet receptors and protein complexes and the signaling pathways involved in platelet IL-1 response. This extends our understanding of the role of platelets in both septic and sterile inflammatory responses. Advisors/Committee Members: McIntyre, Thomas (Advisor).

Subjects/Keywords: Biology; Cellular Biology; Immunology; Molecular Biology; Platelets; Interleukin1; IL-1R1; IL-1beta; microparticles; exosomes; inflammatory response; sterile inflammation

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Narayanan, P. (2014). Interleukin 1 Receptor1 signaling in Platelet Inflammatory responses Interleukin-1ß processing and secretion. (Doctoral Dissertation). Cleveland State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=csu1425911007

Chicago Manual of Style (16th Edition):

Narayanan, Padmini. “Interleukin 1 Receptor1 signaling in Platelet Inflammatory responses Interleukin-1ß processing and secretion.” 2014. Doctoral Dissertation, Cleveland State University. Accessed October 16, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=csu1425911007.

MLA Handbook (7th Edition):

Narayanan, Padmini. “Interleukin 1 Receptor1 signaling in Platelet Inflammatory responses Interleukin-1ß processing and secretion.” 2014. Web. 16 Oct 2019.

Vancouver:

Narayanan P. Interleukin 1 Receptor1 signaling in Platelet Inflammatory responses Interleukin-1ß processing and secretion. [Internet] [Doctoral dissertation]. Cleveland State University; 2014. [cited 2019 Oct 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=csu1425911007.

Council of Science Editors:

Narayanan P. Interleukin 1 Receptor1 signaling in Platelet Inflammatory responses Interleukin-1ß processing and secretion. [Doctoral Dissertation]. Cleveland State University; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=csu1425911007

3. Zahedi-Nejad, Maryam Sadat. CHARACTERISATION OF THE EXPRESSION AND DEGRADATION OF THE PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 1.

Degree: 2012, University of Manchester

Inflammation plays a crucial role in protecting the host from infection and tissue injury. However, uncontrolled inflammation contributes to the pathogenesis of major auto-inflammatory diseases. Interleukin-1 (IL-1), a pleiotropic pro-inflammatory cytokine, is a pivotal mediator of many of these diseases. The best characterised IL-1 family members, IL-1α and IL-1β, are produced as precursor forms of 31 kDa in size. Both precursors are cleaved and secreted, activating transmembrane IL-1 receptors on IL-1-responsive cells. Many studies that focused on IL-1α have shown that the precursor and processed mature Ct peptide, as well as its N terminus (Nt) form, can elicit a signal. However, with IL-1β, only the processed mature Ct form is known to elicit an inflammatory response and no immunological activity has been attributed to Nt fragments of pro-IL-1β. Therefore, the first objective of this study was to produce recombinant human Nt-IL-1β fragments in bacterial and mammalian expression system to investigate their possible immunomodulatory functions. Recombinant His-tagged N-terminus fragments (10 and 14 kDa) of pro-IL-1β were cloned into the bacterial expression vector pET-22(+) and expressed in E. coli BL21(DE3) followed by purification using three consecutive columns (IMAC, SEC and AEC). Purification analysis of eluted proteins from columns indicated that the recombinant proteins were always co-purified with some other bacterial proteins. The Nt fragments of pro-IL-1β were cloned into the mammalian expression plasmid, pcDNA3.1(+). Expression of these proteins was monitored by transfection of two mammalian cell lines: Human Embryonic Kidney (HEK) 293 cells and monkey kidney cells (COS-7). No protein expression was observed with either construct.These limitations urged us to investigate the expression and degradation of endogenous IL-1 in vitro. Previous studies have shown that the transcription of cytokine genes in response to lipopolysaccharide (LPS) is usually rapid and begins to decline within a few hours after stimulation. The proteasome is the major cellular proteolytic apparatus and controls the turn-over of cellular proteins. We investigated the intracellular stability of IL-1α and IL-1β in LPS-stimulated mouse J774 macrophages and primary mouse bone marrow derived macrophages (BMDMs). Exposure of LPS-stimulated J774 and BMDMs to three different classes of proteasome inhibitors (peptide alhedyde (ALLN), peptide boronate (MG262) and non-peptide inhibitor (β-lactone)) prevented the degradation of intracellular IL-1α and IL-1β in a concentration and time dependent manner. Furthermore, the release of IL-1 into the culture media was not affected by any of these inhibitors in LPS-stimulated J774 cells. However, in LPS-stimulated BMDMs, β-lactone increased the release of both IL-1α and IL-1β and ALLN only increased IL-1α release into culture supernatant compared to control. MG262 had no effect on the release of either. These data suggest that the proteasome plays an important role in controlling the amount of IL-1α and… Advisors/Committee Members: PELEGRIN, PABLO P, Brough, David, Pelegrin, Pablo.

Subjects/Keywords: Interleukin1, IL-1α and IL-1β, Proteasome, Proteasome inhibitors Monocytes; LPS

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Zahedi-Nejad, M. S. (2012). CHARACTERISATION OF THE EXPRESSION AND DEGRADATION OF THE PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 1. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159460

Chicago Manual of Style (16th Edition):

Zahedi-Nejad, Maryam Sadat. “CHARACTERISATION OF THE EXPRESSION AND DEGRADATION OF THE PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 1.” 2012. Doctoral Dissertation, University of Manchester. Accessed October 16, 2019. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159460.

MLA Handbook (7th Edition):

Zahedi-Nejad, Maryam Sadat. “CHARACTERISATION OF THE EXPRESSION AND DEGRADATION OF THE PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 1.” 2012. Web. 16 Oct 2019.

Vancouver:

Zahedi-Nejad MS. CHARACTERISATION OF THE EXPRESSION AND DEGRADATION OF THE PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 1. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2019 Oct 16]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159460.

Council of Science Editors:

Zahedi-Nejad MS. CHARACTERISATION OF THE EXPRESSION AND DEGRADATION OF THE PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 1. [Doctoral Dissertation]. University of Manchester; 2012. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159460

.