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Elucidating the Role of WNT5A Signaling in Immune Response and Inflammation using Animal Model

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Title Elucidating the Role of WNT5A Signaling in Immune Response and Inflammation using Animal Model
 
Creator Maiti, George
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description Several lines of evidence suggest that Wnt5a signaling in macrophages plays a significant role in the regulation of cytokine secretion. However, whether or how it also facilitates the coordination of immune response and inflammation that is concomitant with cytokine secretion is unclear at the cellular and molecular level. We are interested in analyzing the influence of Wnt5a signaling on macrophages, which comprise a crucial component of host immune surveillance and inflammation. Phagocytosis by macrophages is a crucial component of innate immune functions which if remains unregulated may enhance inflammation thus leading to pathological conditions. Thus we addressed if Wnt5a, a potential mediator of inflammation stimulates phagocytosis of exogenous antigens by macrophages, and analyzed its effects. In the current investigation we have demonstrated the escalating prevalence of Wnt5a expressing macrophages in the lymph nodes, with increasing inflammation. Our experimental findings, furthermore, reveal that Wnt5a stimulates phagocytosis and associated cell activation through Rac1-PI3 kinase and lipid raft dependent processes. Wnt5a mediated augmentation in phagocytosis is suppressed by blocking expression of the putative Wnt5a receptor Frizzled 5. Enhanced phagocytosis of bacteria by Wnt5a – Fz5 signaling is linked with an upsurge in pro-inflammatory cytokine secretion, but not with an increase in bacterial killing rate. Importantly, a small molecule inhibitor of Wnt production, IWP-2, which reduces secretion of functionally active Wnt5a, not only suppresses both phagocytosis and the secretion of proinflammatory
cytokines, but also accelerates the bacterial killing rate within a limited time frame.
 
Date 2014
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2081/1/Thesis.pdf
Maiti, George (2014) Elucidating the Role of WNT5A Signaling in Immune Response and Inflammation using Animal Model. PhD thesis, Calcutta University.
 
Relation http://www.eprints.iicb.res.in/2081/