Degree Type

Dissertation

Date of Award

1988

Degree Name

Doctor of Philosophy

Department

Genetics, Development and Cell Biology

First Advisor

D. C. Beitz

Abstract

1,25-Dihydroxyvitamin D[subscript]3 (calcitriol) is an immunoregulatory steriod hormone that suppresses interleukin-2 (IL-2) production and inhibits mitogen-induced DNA synthesis in lymphocytes. In these studies, I evaluated the effect of in vitro and in vivo administration of calcitriol on DNA synthesis in bovine peripheral blood mononuclear cells (PBM). Calcitriol inhibited DNA synthesis of in vivo phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-stimulated PBM, but the effects of concanavalin A (ConA)-stimulated PBM were dependent on initial rates of DNA synthesis. PBM from cows with low proliferative response to ConA were stimulated significantly by calcitriol, whereas PBM from cows with high proliferative responses were unaffected by calcitriol addition. DNA synthesis was significantly enhanced by calcitriol when increasing amounts of monocytes were added to low density cultures of nonadherent PBM cells that had low initial proliferative response to ConA. DNA synthesis was inhibited by calcitriol under all conditions of monocyte additions to high density cultures of nonadherent PBM cells that had high initial proliferative response to ConA. Increasing the number of monocytes added, however, significantly attenuated the calcitriol-induced inhibition of DNA synthesis. In vivo administration of calcitriol enhanced in vitro DNA synthesis of PHA- and ConA-induced PBM, and inhibited PWM-induced PBM DNA synthesis. These studies demonstrate that calcitriol induces both stimulatory and inhibitory effects on DNA synthesis of mitogen-induced PBM that are dependent on mitogen, culture conditions, and mode of calcitriol administration;These studies also examined the effect of the bone calcium mobilizing hormones, parathyroid hormone (PTH) and calcitriol, on in vitro monocyte-mediated bond degradation. Monocytes degrade devitalized bone in vitro and are found in areas of bone-resorbing osteoclasts and chronic inflammation. PTH administration increased monocyte-mediated bone degradation, whereas calcitriol administration had no effect. PTH administration also enhanced production of hydrogen peroxide by monocytes on the same day as peak increase of monocyte-mediated bone degradation, thus suggesting an inflammatory-type mechanism for PTH induction of monocyte-mediated bone degradation.

DOI

https://doi.org/10.31274/rtd-180813-13120

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Frank Gerard Edward Hustmyer

Language

en

Proquest ID

AAI8825927

File Format

application/pdf

File Size

146 pages

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