Three bovine casein peptides, LLY, PGPIPN, and TTMPLW, have been reported to stimulate phagocytosis of sheep red blood cells by murine macrophages. TTMPLW also protected mice against Klebsiella pneumoniae infection. The purpose of this study was to investigate the effects of these three peptides on cytokine (TNF-$ alpha$ and IL-6) production and nitric oxide (NO) release by bone marrow macrophages (BMM). The peptides alone were incapable of stimulating cytokine production or NO release in naive or IFN-$ gamma$-primed BMM. However, when BMM were coincubated with the peptides (1.0 $ mu$M) and LPS (100 ng/ml), an augmentative effect on TNF-$ alpha,$ IL-6 and NO production was observed. The peptides increased the response of BMM to stimulation with LPS in a dose- and time-dependent manner. Of the three peptides, TTMPLW (0.01, or 1.0 $ mu$M) had the greatest augmentative effect on NO production by LPS-stimulated BMM. Tumor necrosis factor-$ alpha$ production peaked after 4 hr stimulation, and decreased rapidly thereafter. Among three peptides, TTMPLW induced the highest amount of TNF-$ alpha$ production at a concentration of 1.0 $ mu$M. When used at a concentration as low as 0.01 $ mu$M, TTMPLW and PGPIPN, but not LLY, potentiated TNF-$ alpha$ production. All the peptides (1.0 $ mu$M) stimulated IL-6 production by BMM, which plateaued after 12 hr. The auto/paracrine TNF-$ alpha$ produced by LPS-stimulated BMM was partially responsible for release of NO. After all the TNF-$ alpha$ was neutralized, release of NO was reduced by about 21% (P $<$ 0.01). However, neutralization of IL-1$ beta$ and IL-6 did not have any effect on NO production by LPS-stimulated BMM. These results demonstrate that bovine casein peptides can costimulate naive macrophages with LPS for proinflammatory cytokine production and NO release and may play a role in host defense against pathogens.

This thesis studied the role of spinal nitric oxide (NO) in carrageenan-induced dermal hyperalgesia in the rat hindpaw by means of intrathecal (i.t.) administration of various NO synthase (NOS) inhibitors. A spinal role for NO in carrageenan-induced thermal hyperalgesia was confirmed by dose-dependently reducing the hyperalgesia with a non-selective NOS inhibitor. Next, it was determined that a relatively selective neuronal NOS (nNOS) inhibitor and two relatively selective inducible NOS (iNOS) inhibitors were able to reduce carrageenan-induced thermal hyperalgesia. Finally, early administration of either an nNOS or an iNOS inhibitor had no significant effect on carrageenan-induced thermal hyperalgesia. However, late administration of an iNOS, but not an nNOS inhibitor, significantly reduced the thermal hyperalgesia. We therefore suggest that iNOS contributes to only the late stages of carrageenan-induced thermal hyperalgesia, while nNOS likely plays a role throughout the entire time course of the injury.

No description available.

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / Nitric oxide (NO) plays a fundamental role in vascular homeostasis including vasomotor tone, platelet adhesion and aggregation. The current studies examine various aspects of NO responses, including: the methodology for assessment of vascular NO responses, and identification of factors reponsible for poor responsiveness and pharmacological modulation of these responses. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1277081 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2007

Dissertation (PhD)--University of Stellenbosch, 2007. / Bibliography. Also available via the Internet.

Thesis (Ph.D.)--Tufts University, 2003. / Adviser: Barry A. Trimmer. Submitted to the Dept. of Biology. Includes bibliographical references (leaves 165-178). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Thesis (M.S.)--University of North Texas, Dec., 2007. / Title from title page display. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 192-196).

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.