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The Effects of Aldehydehydrogenase1A1 on Immunoglobulin Production in Mice

Mayeku, Jukie K.

Abstract Details

2010, Master of Science, Ohio State University, Human Ecology: Human Nutrition and Food Management.

Vitamin A and its metabolites, retinoic acid (RA) and retinal, regulate multiple life-sustaining processes including vision, haematopoiesis, skeletal growth, fertility (male and female), embryogenesis, epithelial cell integrity against infections, and immunity. Deficiency in dietary vitamin A in animals leads to severe malfunction of the intestinal enzymes associated with mucosal immunity and decreased immunoglobulin A (IgA) production, or impaired IgA function. In HIV-infected children, supplementation with vitamin A decreases diarrhea and mortality. At present, the mechanisms by which vitamin A exerts its immune function remain poorly understood. Recent studies in animals supplemented with the vitamin A metabolite RA showed increases in IgA levels in mice. RA is generated from retinaldehyde by the aldehyde dehydrogenase-1 family of enzymes (Aldh1) that is comprised of three members: Aldh1A1, A2, and A3. Aldh1A1 is the major cytosolic enzyme involved in RA production. However, the role of Aldh1A1 in the regulation of IgA production has not been investigated. We hypothesize that Aldh1A1 affects immunoglobulin production in mice.

We studied the effect of Aldh1A1 on IgA production in Aldh1A1-/- and WT mice on either a normal chow diet or a high-fat diet. Enzyme-linked immunosorbent assay (ELISA) was used to measure IgA and IgG levels in the plasma, spleen, and feces. Western blot was used to estimate IgA heavy chain and light kappa and lambda chains in spleen. Using ELISA, we demonstrated that IgA levels in plasma were significantly higher (292%) in Aldh1A1-/- (n=12) than WT (n=8) mice on regular chow. Plasma IgG levels were moderately higher in Aldh1A1-/- (127%) than in WT. Next we examined whether Aldh1A1 deficiency influences immunoglobulin production in major sites of immunoglobulin production by B cells. We found several abnormalities in the spleen of Aldh1A1 deficient mice. Aldh1A1-/- spleens were enlarged 120% as compared to WT mice. There were higher levels of spleen IgA (162%) in Aldh1A1-/- than in WT with a higher expression of light IgA kappa chains. Spleens had (307%) higher IgG levels in Aldh1A1-/- than WT mice. Fecal samples were used to investigate the effects of Aldh1A1 on immunoglobulin production at mucosal sites. Fecal IgA levels were the same in both groups. Significantly higher amounts of fecal IgG (4000%) were found in Aldh1A1-/- as compared to WT mice.

A high fat diet appeared to additional influence immunoglobulin production. The Aldh1A1 dependent changes in immunoglobulin production were augmented by a high-fat diet. In high fat diet fed animals, plasma had 575% and 741% higher levels of IgA and IgG in Aldh1A1-/- than WT respectively. Spleens had (297%) higher IgG levels in Aldh1A1-/- mice as compared to WT. Both plasma and spleens expressed higher protein levels of light kappa chain in Aldh1A1 -/- than in WT mice on a high-fat diet. Our data reveal that the Aldh1A1 enzyme suppresses immunoglobulin A and G production and plays a significant role in the regulation of immunoglobulins light chain levels in response to diet.

Earl H. Harrison, PhD (Advisor)
Ouliana Ziouzenkova, PhD (Advisor)
Tracey L. Papenfuss, DVM,MS,PhD (Committee Member)
40 p.

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Citations

  • Mayeku, J. K. (2010). The Effects of Aldehydehydrogenase1A1 on Immunoglobulin Production in Mice [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1281035253

    APA Style (7th edition)

  • Mayeku, Jukie. The Effects of Aldehydehydrogenase1A1 on Immunoglobulin Production in Mice. 2010. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1281035253.

    MLA Style (8th edition)

  • Mayeku, Jukie. "The Effects of Aldehydehydrogenase1A1 on Immunoglobulin Production in Mice." Master's thesis, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1281035253

    Chicago Manual of Style (17th edition)