TNF-α, IL-1 and PGE2 Secretion Following Macrophage Activation by Mycoplasma Capricolum Membranes
Macrophages play an important role in the body’s defence against microbial infections and neoplasia. Activation of macrophage to selectively kill tumor cells is the result of interaction with various microbial products and cytokines (1, 2, 3). Several cytotoxic factors secreted from activated macrophage have been described, the most important among them is tumor necrosis factor α (TNF-α) (5). Other factors implicated in macrophage-mediated tumor cell cytotoxicity are: interleukin-1 (IL-1) (6), cytolytic serine proteases, reactive oxygen products, arginase, lysosomal enzymes and the complement factor C3a (7). TNF-α causes hemorrhagic necrosis when injected into tumor bearing mice and is also toxic to certain tumor cell lines in vitro The common potent inducer of TNF-α is bacterial LPS (6). IL-1 apart from contributing to macrophage-mediated cytolysis, is a major regulator of T lymphocyte proliferation (8). Macrophage were shown to remain only transiently activated, such that the induced tumor cytotoxicity is rapidly lost (9, 10). This led to the suggestion that a negative feedback regulation may exist and that prostaglandin E2 (PGE2) may represent an endogenous regulator that shuts off macrophage activation once it has developed (11). Since LPS, the common inducer of TNF-α and IL-1, is highly toxic in human and animals (5, 12), attempts are directed at finding a non-toxic substitute. We recently found that membranes of Mycoplasma capricolum, a non-toxic mycoplasma which contain no LPS (13), induce TNF-a-mediated tumor cell killing following murine bone marrow macrophage (BM-macrophage) activation (14, 15). In the work presented herein, we describe the potency of M. capricolum membranes to induce TNF-α, IL-1 and PGE2 secretion following BM-macrophage activation. We discuss the exerted effects of M. capricolum membranes on the immune system and their therapeutic potential in treatment of malignant diseases.
KeywordsTumor Cell Killing PGE2 Concentration Mediate Tumor Cell PGE2 Secretion Mycoplasma Capricolum
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