Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep34145
Title: Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists
Authors: Ang, Zhiwei 
Er, Jun Zhi 
Tan, Nguan Soon 
Lu, Jinhua 
Liou, Yih-Cherng 
Grosse, Johannes
Ding, Jeak Ling 
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
PROTEIN-COUPLED RECEPTOR
NF-KAPPA-B
GUT MICROBIOTA
INFLAMMATORY RESPONSES
GPR43
GPCR
FERMENTATION
PROPIONATE
EXPRESSION
DISEASE
Issue Date: 26-Sep-2016
Publisher: NATURE RESEARCH
Citation: Ang, Zhiwei, Er, Jun Zhi, Tan, Nguan Soon, Lu, Jinhua, Liou, Yih-Cherng, Grosse, Johannes, Ding, Jeak Ling (2016-09-26). Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists. SCIENTIFIC REPORTS 6 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/srep34145
Abstract: Knockout mice studies implicate the mammalian short-chain fatty acid (SCFA) receptors, FFAR2 and FFAR3- in colitis, arthritis and asthma. However, the correlation with human biology is uncertain. Here, we detected FFAR2 and FFAR3 expression in human monocytes via immunohistochemistry. Upon treatment with acetate SCFA or FFAR2- and FFAR3-specific synthetic agonists, human monocytes displayed elevated p38 phosphorylation and attenuated C5, CCL1, CCL2, GM-CSF, IL-1α, IL-1β and ICAM-1 inflammatory cytokine expression. Acetate and FFAR2 agonist treatment also repressed Akt and ERK2 signalling. Surprisingly, mouse monocytes displayed a distinct response to acetate treatment, elevating GM-CSF, IL-1α, and IL-1β cytokine expression. This effect persisted in FFAR2/3-knockout mouse monocytes and was not reproduced by synthetic agonists, suggesting a FFAR2/3 independent mechanism in mice. Collectively, we show that SCFAs act via FFAR2/3 to modulate human monocyte inflammatory responses- a pathway that is absent in mouse monocytes.
Source Title: SCIENTIFIC REPORTS
URI: https://scholarbank.nus.edu.sg/handle/10635/193723
ISSN: 20452322
DOI: 10.1038/srep34145
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