Graduation Year

2008

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Molecular Medicine

Major Professor

Shyam S. Mohapatra, Ph.D.

Co-Major Professor

Richard Heller, Ph.D.

Keywords

Immunology, Turmeric, Cytoskeleton, Inflammation, Immune Suppression

Abstract

Curcumin is the yellow pigment found in the Indian spice curry. It has anti-inflammatory, ant-oxidant, anti-cancer, anti-viral, anti-bacterial and wound healing properties. It is widely used in industry for its flavor as a spice and as a coloring agent because of its brilliant yellow color. It is also used as a dye for textiles and as an additive to cosmetics. Dendritic cells (DCs) are the sentinels of the immune system and functions as the bridge between the innate and adaptive immune response. The effect of curcumin on DCs is poorly understood. A study shows curcumin prevents the immuno-stimulatory function of bone marrow-derived murine DCs, but no study examines the effects on human DCs. This study investigates the effects of curcumin on immature human DC maturation and function in response to immune stimulants lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (poly I:C).

Human CD14+ monocytes isolated from the peripheral blood of donors are cultured with GM-CSF and IL-4 supplemented media to generate immature DCs. The cultures are treated with curcumin, stimulated with the above mentioned stimulants then functional assays performed. These assays include homotypic cluster formation, surface marker expression, cytokine production, chemotaxis, endocytosis, DC-induced allogeneic CD4+ T cell proliferation after mixed lymphocyte reaction, gene expression analysis and immuno-fluorescence labeling and imaging. Curcumin-induced changes in gene expression indicate the actin cytoskeleton signaling pathway is a target. Immuno-fluorescence labeling and imaging of f-actin was carried out. Curcumin reduces DC maturation in response to the stimulants used in the study. Expression of surface markers, cytokines and chemokines is reduced as well as DC-induced stimulation of allogeneic CD4+ cells after MLR.

Curcumin prevents chemotaxis without affecting chemokine receptor expression and significantly reduces endocytosis in non-stimulated cells. Curcumin-treated DCs do not induce a Th1 or Th2 population in allogeneic MLR but induces a CD25+Foxp3+ regulatory cell population. Immuno-fluorescence imaging shows curcumin causes the cell to become more rounded. These data imply that curcumin inhibits f-actin polymerization and thereby prevents DC maturation and function in response to stimulation. This outlines a novel role for curcumin as an immune suppressant and shows its therapeutic potential as an anti-inflammatory agent.

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