No abstract

No abstract

No abstract

Initial activation is likely followed by the activation of the JNK and p38 MAPK signal transduction pathways resulting in activation, release, and translocation of transcription factor nuclear factor κB (Nf-κB). This dissertation research study represents the first indepth study into characterizing the bioactive component(s) of commercial shark cartilage responsible for its immunomodulating properties and defining cellular responses at the molecular level.

The erosion and breakdown of cartilage is generally recognized to be an integral manifestation of arthritic disease, which is often accompanied by the development and progression of inflammation associated with it. Commercial shark cartilage (SC) is a popular dietary supplement taken for the prevention and/or control of chronic disease, including arthritis. The efficacy of SC in maintaining joint health remains questionable; there is a lack of sufficient reliable information on its effect on immunocompetent cells, and the potential health risks involved have not been adequately assessed. Our earlier in vitro studies showed that SC extracts induce a Th1-type inflammatory cytokine response in human leucocytes, and collagen type II alpha 1 protein was shown to be an active cytokine-inducing component in SC. In this study, we further define the cellular response to SC stimulation by classifying leucocytes into primary and secondary responders employing enriched leucocyte subpopulations. Inhibitors of specific signaling pathways were used to verify the functional effect of SC on specific pathway(s) utilized. Results indicate the monocyte/macrophage as the initially responding cell, followed by lymphocytes and the production of interferon-γ. Chemokines, MCP-1 and RANTES, were produced at significant levels in stimulated leucocyte cultures. Initial cellular activation is likely followed by activation of Jun Kinase and p38 mitogen-activated protein kinase signal transduction pathways. This study presents evidence of significant immunological reactivity of components of commercial SC supplement, which could pose a potential health risk for consumers, particularly those with underlying inflammatory disease such as irritable bowel syndrome and arthritis.