Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists.
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.
NUS graduate School for Integrative Science and Engineering, National University of Singapore, 117543 Singapore.
Zhiwei
Z
Ang
NUS graduate School for Integrative Science and Engineering, National University of Singapore, 117543 Singapore.
Jun Zhi
JZ
Er
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637511, Singapore.|Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673 Singapore.
Nguan Soon
NS
Tan
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore.
Jinhua
J
Lu
Department of Biological Sciences, Faculty of Science, National University of Singapore, 117543 Singapore.
Yih-Cherng
YC
Liou
Takeda Cambridge Limited, 418 Cambridge Science Park, Milton Road, Cambridge, CB4 0PA, UK.
Johannes
J
Grosse
Department of Biological Sciences, Faculty of Science, National University of Singapore, 117543 Singapore.
Jeak Ling
JL
Ding
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