miR-146a Upregulation of phagocytosis in Human Macrophage Sjögren's Syndrome Model

Type of Submission

Poster

Keywords

Sjögren's, macrophage, phagocytosis, miR-146a

Abstract

Sjögren's syndrome (SjS) is an autoimmune disease that attacks exocrine glands such as salivary and lacrimal glands resulting in severe dryness of the mouth and eyes. Previous studies discovered increased microRNA-146a (miR-146a) expression in peripheral blood mononuclear cells in SjS patients compared to healthy controls. Like all microRNAs, miR-146a negatively regulates specific genes through binding mRNA, leading to degradation or translational inhibition. Further investigation into the role of increased miR-146a expression in SjS revealed links several immune functions including cytokine production, cellular migration and phagocytosis. The objective of this study was to further examine the relationship between miR-146a expression and the rate of phagocytosis in human macrophages. We hypothesized that increased expression of miR146a leads to upregulation of phagocytic activity. The study was conducted by transfecting human monocyte THP-1 cells with synthetic miR-146a. qRT-PCR was used to detect successful transfection of miR-146a into the cells. Phorbol myristate acetate (PMA) treatment differentiated monocytes into mature macrophages. Phagocytic activity was determined using a phagocytosis assay in which mock-transfected (control) and miR-146a-transfected cells were incubated with fluorescently labeled E. coli for five hours. A fluorescent plate reader was used to measure fluorescence intensity after five hours of incubation. Our results showed miR-146a expression at a level 13,000-fold higher in transfected cells compared to mock cells, indicating successful transfection of the synthetic miR-146a into cells. Phagocytic activity of the miR-146a transfected cells increased by 50.9% (n=3, p<0.0001) compared to mock-transfected cells, supporting our hypothesis. Further research may reveal the mechanism by which miR-146a upregulates phagocytosis. More studies are required to investigate the link between monocyte phagocytosis and SjS pathogenesis.

Faculty Sponsor or Advisor’s Name

Dr. Kaleb Pauley

Campus Venue

Stevens Student Center

Location

Cedarville, OH

Start Date

4-1-2015 11:00 AM

End Date

4-1-2015 2:00 PM

Comments

Best Poster Presentation in Category 1: Controlled Experimental Studies

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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Apr 1st, 11:00 AM Apr 1st, 2:00 PM

miR-146a Upregulation of phagocytosis in Human Macrophage Sjögren's Syndrome Model

Cedarville, OH

Sjögren's syndrome (SjS) is an autoimmune disease that attacks exocrine glands such as salivary and lacrimal glands resulting in severe dryness of the mouth and eyes. Previous studies discovered increased microRNA-146a (miR-146a) expression in peripheral blood mononuclear cells in SjS patients compared to healthy controls. Like all microRNAs, miR-146a negatively regulates specific genes through binding mRNA, leading to degradation or translational inhibition. Further investigation into the role of increased miR-146a expression in SjS revealed links several immune functions including cytokine production, cellular migration and phagocytosis. The objective of this study was to further examine the relationship between miR-146a expression and the rate of phagocytosis in human macrophages. We hypothesized that increased expression of miR146a leads to upregulation of phagocytic activity. The study was conducted by transfecting human monocyte THP-1 cells with synthetic miR-146a. qRT-PCR was used to detect successful transfection of miR-146a into the cells. Phorbol myristate acetate (PMA) treatment differentiated monocytes into mature macrophages. Phagocytic activity was determined using a phagocytosis assay in which mock-transfected (control) and miR-146a-transfected cells were incubated with fluorescently labeled E. coli for five hours. A fluorescent plate reader was used to measure fluorescence intensity after five hours of incubation. Our results showed miR-146a expression at a level 13,000-fold higher in transfected cells compared to mock cells, indicating successful transfection of the synthetic miR-146a into cells. Phagocytic activity of the miR-146a transfected cells increased by 50.9% (n=3, p<0.0001) compared to mock-transfected cells, supporting our hypothesis. Further research may reveal the mechanism by which miR-146a upregulates phagocytosis. More studies are required to investigate the link between monocyte phagocytosis and SjS pathogenesis.