Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/119858
Title: ELUCIDATING THE FUNCTIONS OF GPR43 AND GPR41 IN MONOCYTES
Authors: ANG ZHIWEI
Keywords: GPR43, GPR41, Monocyte, Immunity, Cytokine, Signaling
Issue Date: 22-Jan-2015
Citation: ANG ZHIWEI (2015-01-22). ELUCIDATING THE FUNCTIONS OF GPR43 AND GPR41 IN MONOCYTES. ScholarBank@NUS Repository.
Abstract: The fermentation of dietary fiber by the gut microbiota produces short-chain fatty acids (SCFAs), namely acetate, propionate and butyrate. These SCFAs activate the human G protein-coupled receptors: GPR41 and GPR43. Here, we fully characterize the human GPR43 promoter, identifying XBP1 as a core cis element which is activated by stimuli such as LPS, GM-CSF and TNF to induce GPR43 expression in monocytes. Next, we defined the role of GPR43 and the related SCFA receptor, GPR41, in monocytes. Wildtype and GPR43/41 knockout monocytes were cultured ex vivo and treated with synthetic GPR43/41 agonists. These assays confirmed that the SCFA, acetate, acts via GPR43 and GPR41 to repress inflammatory cytokine expression and signaling in human monocytes. Surprisingly, these GPR43/41 inhibition pathways were absent in mice monocytes, resulting in a distinct response to acetate. Collectively, we reveal that GPR41 and GPR43 modulate human monocytes cytokine expression.
URI: http://scholarbank.nus.edu.sg/handle/10635/119858
Appears in Collections:Ph.D Theses (Open)

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