Maturing DCs involved in innate or adaptive immunity are also an abundant source of chemokines in a precise time-ordered fashion. After stimulation with a microbial antigen, DCs have an initial burst of MlP-la (CCL3), MlP-1b (CCL4) and lL-8 (CXCL8) production within a few hours. RANTES (CCL5) and MCP-1 are also induced but in a more steady manner. At a later time point DCs produce mainly lymphoid chemokines such as CCLl7 (TARC), CCLl8 (DC-CDl), CCLl9 (MIP-3B) and CCL22 (MDC) that attract T and B lymphocytes (McColl, 2002; Sallusto et al., 2000). A recent study by our laboratory showed that Lp induced upregulation of the early inflammatory mediators such as CCL3, RANTES and MCP-1, while EGCG effect in a dose-dependent manner inhibited the upregulation of these molecules (Matsunaga et al., 2001a).
Again, the inhibitory effects of EGCG on important parameters, such as DC maturation and production of proinflammatory cytokines and chemokines, like lL-12 and MCP-1 is seemingly contradictory given reports demonstrating antimicrobial effectiveness of EGCG. Perhaps the answer to this seemingly apparent contradiction lies in EGCG effectiveness as an innate immune stimulatory by mechanisms such as upregulation of phagocytic capacity of phagocytic cells like macrophages and DCs, as well as certain proinflammatory cytokines like TNFa, crucial for an effective immune response.
It is also important to note that upregulation of various parameters often associated with a heightened immune response is not always beneficial to the host in combating microbial infection. Sepsis is a severe and systemic illness caused by the excessive inflammatory response to microbial infections, often with fatal results. Both Gram-negative and Gram-positive bacterial infections are capable of causing sepsis. In this respect, medicinal properties of plant-derived agents need to be considered from the aspect of not only their ability to stimulate immune activity but also their possible role in downregulating excessive inflammatory responses. Ginsan, an acidic polysaccharide prepared from Panax ginseng appears particularly effective in this regard. Mice treated with ginsan before bacterial challenge with Staphylococcus aureus (S. aureus) are reportedly highly protected from sepsis-induced death while still maintaining antibacterial capacity. Interestingly, the phagocytic activity of ginsan-treated macrophages was shown to be considerably enhanced against S. aureus. At the same time, the synthesis of inflammatory cytokines such as IL-12 was significantly downregulated at the early phase of sepsis in the mice treated with ginsan before bacterial challenge (Ahn et al., 2006).
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