Macrophages
Macrophages play a crucial role in innate immunity and also help initiate adaptive immunity.131,132 Macrophages predominantly expressing the killer phenotype are called M1 macrophages, whereas those involved in tissue repair are called M2 macrophages.133 The primary role of macrophages is to phagocytose or engulf and then digest cellular debris and pathogens; they also stimulate lymphocytes and other immune cells to respond to pathogens. M1 macrophages are activated by LPS and IFN-γ and secrete high levels of IL-12 and low levels of IL-10; and M2 macrophages produce high levels of IL-10, TGF-β, and low levels of IL-12.133 IL-12 is involved in the stimulation and maintenance of Th1 cellular immune responses and also has an important role in enhancing the cytotoxic function of NKs. Macrophages can be identified by specific expression of a number of proteins including CD14, CD40, CD11b, CD64, F4/80 (mice)/EMR1 (human), lysozyme M, MAC-1/MAC-3, and CD68. LBPs are able to activate macrophages. A study found that LBPs (50 mg/kg, ip) markedly upregulated the expressions of CD40, CD80 (B-lymphocyte activation antigen B7-1), CD86 (B-lymphocyte activation antigen B7-2), and MHC-II molecules on peritoneal macrophages. In vitro studies showed that LBPs activated transcription factors NF-κB and AP-1, induced TNF-α, IL-1β, and IL-12p40 mRNA expression, and enhanced TNF-α production in RAW264.7 macrophage cells in a dose-dependent manner.134 Furthermore, LBPs significantly enhanced macrophage endocytic and phagocytic capacities in vivo. These results indicated that LBPs enhance innate immunity by activating macrophages. The mechanism might be through activation of transcription factors NF-κB and AP-1 to induce TNF-α production and upregulation of MHC-II co-stimulatory molecules.134
An in vitro study by Teng et al135 investigated the inhibitory effects of LBPs on the production of LPS-induced proinflammatory mediators in BV2 microglia. The data showed that LPS induced the activation of NF-κB and its upstream protein caspase 3. NF-κB plays a key role in inflammatory disease and may be involved in autophagy, while autophagy itself may also participate in the pathogenesis of inflammation and inflammatory disease.136 LPS also unregulated the expression of an additional apoptosis-inducing factor with a passive role in the maturation of caspase processing, HSP60, in BV2 microglial cells and increased the release of TNF-α and HSP60 in the culture media. Following treatment with LBPs, the activated caspase 3 were significantly suppressed. Furthermore, the enhanced expression of HSP60 was reduced and the LPS-induced release of TNF-α and HSP60 was inhibited. These results suggest that LBPs may have therapeutic potential for the treatment of neurodegenerative diseases that are accompanied by microglial activation.
Peng et al137 investigated the effect of Lycium ruthenicum polysaccharides (LRGP3) on inflammatory reactions induced by LPS in mouse macrophage RAW264.7 cells. The results showed that LRGP3 treatment significantly inhibited the LPS-induced NO production and the mRNA expression of iNOS, as well as the level of TLR4. Furthermore, LRGP3 treatment prevented IκBα degradation and reduced phospho-NF-κB p65 protein expression in LPS-stimulated RAW264.7 cells.137 Meanwhile, the levels of proinflammatory cytokines, such as IL-1α, IL-6, and TNF-α, were suppressed by LRGP3 in LPS-stimulated RAW264.7 cells. LRGP3 attenuated LPS-induced inflammation via inhibiting TLR4/NF-κB signaling pathway.