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

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.