The Effect of All-trans Retinoic Acid on Macro. Polar

Friday, February 12, 2016
Courtney Smith, University of Nebraska-Medical Center High School Alliance, Bellevue, NE
Obesity is characterized by persistent inflammation, which is a risk factor for developing Type II
diabetes. Macrophages are a major type of immune cell that are important for maintaining tissue
function and responding to injury. Macrophages can be polarized into two phenotypes,
inflammatory (M1) and non-inflammatory (M2). A prolonged presence of M1 macrophages can
lead to organ dysfunction and disease. All--Trans retinoic acid (ATRA) is an agent that was
observed to reduce inflammation in obesity, but it is unknown if ATRA was acting directly on
macrophages. Our hypothesis is that the ATRA treatment will reduce the inflammatory, M1
macrophage phenotype, while promoting the noninflammatory, M2. To test this hypothesis, we
used RAW 264.7, -a non-polarized mouse macrophages cell line that can be induced to adopt the
M1 phenotype by using interferon gamma (IFN-gamma) and lipopolysaccharide (LPS), or to the
M2 phenotype with interleukins (IL-)  4 and 13. The effect of ATRA was measured by
comparing the gene expression levels of the M1 marker IL-6, and the M2 marker arginase-1
(Arg-1) of cells that were treated and not with ATRA. The results showed that ATRA reduced
the expression of IL-6 in M1 cells and increased Arg-1 expression in M2. Furthermore, ATRA
increased Arg-1 gene expression in nonpolarized cells. This findings suggest that ATRA acts to
suppress the inflammatory M1 phenotype, while promoting the M2 phenotype. Therefore, ATRA
may be a potential treatment for diseases that are characterized by increased number of
inflammatory macrophages.