The effect of cabergoline treatment on the expression of inflammatory and anti-inflammatory factors in monocyte-derived dendritic cells

Abstract

Dendritic cells are important antigen-presenting cells that play an essential role in bridging between innate and acquired immune responses. In addition to the exceptional capacity of antigen presentation, these cells are able to initiate and control immunogenic and tolerogenic immune responses. Immunogenic DCs interact with T lymphocytes and play a role in defense against cancer cells, and tolerogenic DCs participate in suppressing immune responses by producing and expressing inhibitory factors. Today, cancer has affected all societies. Considering the side effects of common cancer treatments, including surgery, chemotherapy, and radiation therapy, such as damage to healthy body cells, the use of immunotherapy in the treatment of cancer by improving the function of the immune system has received attention in recent years. On the other hand, the defect in self-antigen tolerance leads to immune reactions against self-antigens, which leads to autoimmune diseases. As a result, specific immune suppression methods can be used in the treatment of autoimmune diseases. Dopamine (DA) is an important neurotransmitter that has recently been shown to be an immunomodulatory mediator, and many immune cells such as DCs express dopamine receptors (DRs). Cabergoline is a dopamine receptor agonist that appears to play an anti-inflammatory role in the immune system. This study investigated the effect of cabergoline drug treatment on the expression of inflammatory and anti-inflammatory factors in monocyte-derived dendritic cells. Methods: First, peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll solution. Then, monocytes were separated from PBMC and using IL-4 and GM-CSF cytokines, monocyte-derived DCs were produced. Expression of surface markers of DCs such as CD11c, HLA-DR and CD86 was performed by flow cytometry. DCs were then incubated with lipopolysaccharide to mature and activate. In order to obtain the best dose of cabergoline drug, doses of 10 and 100 μM were investigated, then the amount of apoptosis and necrosis induced by different doses was measured with Annexin and PI and read by flow cytometry. Then mDCs were treated with cabergoline drug and the relative expression of IL-10, IL-12, TNF-α, TGF-β, NF-KB and IDO genes was obtained by Real Time PCR method. Results: The expression of CD86 and HLA-DR, which are markers related to maturation and antigen presentation, respectively, were significantly increased in DCs treated with cabergoline. The level of TGF-β, IL-10 and IDO in the DCs of the cabergoline group was significantly decreased, while the expression of TNF-α and IL-12 was increased in this group.