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UBC Theses and Dissertations

The role of SHIP2 in suppressing inflammatory signaling induced by LPS in immortalized murine macrophage cell line Wang, Tianren


Inflammation is an important step in the body’s defense against pathogen infection. However, it must be tightly regulated and appropriately terminated to prevent pathological consequences. Interleukin-10 (IL10) is one of the body’s most important anti-inflammatory cytokine that can inhibit many molecular events necessary for promoting inflammation including production of pro-inflammatory cytokines such as Tumor Necrosis Factor α (TNFα). Our laboratory has recently shown that SH2-domain containing Inositol 5ʹ phosphatase (SHIP1) is involved in IL10 signaling in macrophages, and although the mechanism of how this occurs is not well studied, our laboratory have obtained data suggesting SHIP1 mediates IL10 signalling through its phosphatase activity or interaction with other signalling proteins. SHIP2 is the only other known homologue of SHIP1 with approximately 38% amino acid sequence identity, yet they possess several similar functions including mediating FcγIIB signaling and phagocytosis. Because of their similarities and SHIP1’s involvement in IL10 signaling, we sought to investigate whether SHIP2 is also involved in inhibiting inflammatory response in macrophage by knocking it out using CRISPR/Cas9-mediated genome editing. Overall, we were unable to determine whether SHIP2 plays a role in macrophage anti-inflammatory response due to the large variation in cell sensitivity to IL10 and we also observed that transduction of macrophages with CRISPR/Cas9 virus alters the cellular response to IL10 which confounded our investigation of SHIP2 function.

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