JOURNAL ARTICLE

Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells

Tyler J Wenzel, Ellen J Gates, Athena L Ranger, Andis Klegeris
Molecular and Cellular Neurosciences 2020 April 22, : 103493
32333962
Neuroinflammation contributes to neurodegenerative disorders, including Alzheimer's disease (AD). Gut microbes are involved in regulating systemic inflammation. Short-chain fatty acids (SCFAs), which are among the many metabolites released by gut microbes, can cross the blood-brain barrier (BBB) and interact with microglia. High concentrations of individual SCFAs decrease the inflammatory responses of peripheral monocytes; therefore, we hypothesized that SCFAs act on their own or in combinations to reduce the inflammatory response of microglia. Cultured human THP-1 monocytic cells and differentiated human HL-60 myelomonocytic cells were used to model select immune functions of human microglia. Acetate, propionate, butyrate, formate, and valerate were added to cells alone or as a mixture containing SCFAs at an approximate physiological concentration ratio. The SCFA mixture, as well as several individual SCFAs at the highest concentrations used in the mixture (15-236 μM), decreased the secretion of interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and cytotoxins by immune-stimulated THP-1 cells. GLPG 0974, a free fatty acid receptor (FFAR) 2/3 antagonist, did not block the inhibitory effect of the SCFA mixture on IL-1β secretion by THP-1 cells while blocking the inhibitory effect of formate alone. We demonstrated that formate and valerate alone reduced the phagocytic activity of immune-stimulated THP-1 cells. Formate, but not valerate, alone also inhibited the N-formylmethionine-leucyl-phenylalanine (fMLP)-induced respiratory burst of HL-60 cells, reducing the production of reactive oxygen species (ROS). Our data indicate that SCFAs could regulate select microglial functions that are disrupted in AD.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
32333962
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"