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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.24048 |
| Date | January 1996 |
| Creators | Xiao, Chaowu, 1962- |
| Contributors | Zhao, Xin (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Animal Science.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001538431, proquestno: MM19858, Theses scanned by UMI/ProQuest. |
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