LPS decreases the expression of Monocarboxylate transporter‐1 (MCT1) in mouse monocytes

Abstract

The molecule Toll‐like Receptor‐4 (TLR4) recognizes Gram negative bacteria, specifically the lipopolysaccharide component (LPS) and initiates a signal transduction cascade leading to an inflammatory response. Recent studies by this laboratory suggest the cell adhesion glycoprotein Basigin (CD147) interacts with TLR4 via their transmembrane domains. The role of Basigin in mouse retina has been well‐studied and includes an association with Monocarboxylate Transporter 1 (MCT1) for metabolic support of photoreceptor neurons. The role of Basigin in innate immune responses is less‐well studied. Therefore, the response of Basigin to LPS was assessed and compared to that of TLR4. The response of MCT1 to LPS was also assessed. It was hypothesized that Basigin and MCT1 expression would increase in response to LPS. To test this, RAW 264.7 mouse monocytes were incubated in the presence of 1 mg/mL LPS in serum‐free medium for various times ranging from 2–24 hours. Control cells received PBS. The cells were collected, and RNA was isolated for gene expression analyses via quantitative‐reverse transcription PCR (q‐RT‐PCR). The expression of TLR4 decreased at 2 hours and increased at 24 hours of LPS induction, when compared to control samples, although no changes were determined to be statistically significant. The expression of Basigin was similar between control and LPS‐treated cells at all time points, except for 24 hours of induction, when Basigin expression was significantly lower in LPS‐treated cells. MCT1 expression was also similar between control and LPS‐treated cells at all time points, except for 24 hours of induction, when MCT1 expression was significantly lower in LPS‐treated cells. These findings do not support the hypothesis. The data for TLR4 expression in response to LPS in mouse monocytes are consistent with published reports. Although it was hypothesized that metabolic responses would increase in monocytes to support immune mechanisms, the data for MCT1 suggests that metabolism is reduced in activated monocytes, perhaps as a shift of resources from general cellular maintenance to induction of an innate immune response. The observed decrease in Basigin expression also did not support the hypothesis and suggests that the molecule is either regulated directly by the innate immune response or indirectly via its role in metabolism through MCT1. Future studies will assess the expression of Basigin and MCT1 at the protein level to better analyze the role of metabolism in the innate immune response.Support or Funding InformationUNF Office of Academic AffairsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.