Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614557
Title: TREM-2 expression and regulation in inflammation and ischaemia
Author: Bradley, Jenna
ISNI:       0000 0004 5366 808X
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2014
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Abstract:
Triggering receptor expressed on myeloid cells – 2 (TREM-2) is a receptor expressed mainly in myeloid cells. TREM-2 is involved in the resolution of inflammation through dampening Toll-like receptor (TLR) induced pro-inflammatory cytokine secretion and phagocytic functions. It is increased in inflammatory conditions including rheumatoid arthritis and stroke and also in wound healing. However, little is known about how its expression is regulated. This study analysed the expression of TREM-2 in various myeloid and non-myeloid cell types and investigated the regulation of TREM-2 expression in myeloid cells. TREM-2 was expressed in the Golgi apparatus of microglial cells. Several non-myeloid cell types also expressed TREM-2, including bronchial epithelial cells where it was located on cilia in healthy and diseased lung tissues. In THP-1 cells, the anti-inflammatory cytokines interleukin-4 and transforming growth factor-β1 (TGF-β1) induced TREM-2 expression through phosphoinositide 3-kinase (PI3K) and PI3K/ p38 MAP kinase signalling pathways respectively. TGF-β1-induced TREM-2 also required extracellular signal-regulated kinase 1/2 post-translationally for protein expression. Interestingly, TREM-2 was required for TGF-β1-induced matrix metalloproteinase (MMP)-1 expression, the most characterised MMP in wound healing, suggesting that TREM-2 may be required for the beneficial effects of TGF-β1 on wound healing by regulating MMP-1. An in vitro model of ischemia in stroke was then established to study the mechanisms of TREM-2 regulation in stroke. Oxygen glucose deprivation (OGD) had no direct effect on TREM-2 in N9 microglial cells. However, co-culture with healthy neurons reduced microglial TREM-2 expression, which was abolished in co-culture with OGD neurons, suggesting that in the healthy brain, microglial TREM-2 expression is suppressed by neurons, and this suppression is lost during ischaemia, increasing TREM-2 expression. In conclusion, this study characterised TREM-2 expression in non-myeloid cells and identified novel mediators and signalling pathways that regulate TREM-2 expression, which may be responsible for TREM-2 overexpression in inflammatory and ischemic conditions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.614557  DOI: Not available
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