Abdirassil, Aizat
(2024)
The role of disaccharides trehalose and lactotrehalose in macrophage polarization.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Macrophages are essential cells of the innate immune system, engaging in many functions, such as phagocytosis of pathogens and apoptotic cells, initiation and resolution of inflammation and tissue repair. Due to the vast diversity of processes they participate in, macrophages possess remarkable functional plasticity. A commonly accepted spectrum of macrophage activation, also referred to as polarization, has two distinct phenotypes at the far ends of the spectrum – pro-inflammatory M1 and anti-inflammatory M2. M1 macrophages help the organism fight foreign invaders by secreting pro-inflammatory cytokines to recruit various immune cells into the site of inflammation and directly killing pathogens by secreting reactive oxygen and nitrogen species and engulfing them. Meanwhile, M2 macrophages secrete cytokines that reduce inflammation and promote wound healing. In homeostasis, phenotypically distinct macrophages have balanced actions to maintain healthy biological processes. However, in pathogenesis, polarization may be skewed in one direction to promote disease progression. In organ fibrosis, macrophages assume M2 phenotype that secretes TGF-β, the main factor to drive quiescent mesenchymal cells to differentiate into activated myofibroblasts. One therapeutic strategy would be to reprogram M2 macrophages in fibrosis into pro-inflammatory M1 phenotype.
Here, we studied the effect of disaccharide trehalose and its non-hydrolysable isomer, lactotrehalose, on macrophage polarization. We found that these sugars inhibited M2 polarization in vitro. Upon transcriptomic analysis by RNA sequencing, we found that trehalose- or lactotrehalose-treated M2 macrophages showed induced inflammatory signaling pathways, with upregulation of inflammatory cytokines. Future directions include the study of the possible trehalose-recognizing lectin, coded by Clec4e, on macrophages and subsequent activation NF-κB signaling pathway.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
4 December 2024 |
| Date Type: |
Publication |
| Defense Date: |
19 November 2024 |
| Approval Date: |
4 December 2024 |
| Submission Date: |
22 November 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
39 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
macrophage polarization, trehalose, lactotrehalose, inflammation |
| Date Deposited: |
04 Dec 2024 17:58 |
| Last Modified: |
04 Dec 2024 17:58 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47123 |
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