BackgroundChronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine.MethodsWe confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change.ResultsLPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naïve macrophages, through the treatment with high concentrations of cordycepin (40 µg/ml). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-1β, TNF-α) and chemokines (CX3CR1, RANTES), as well as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-β) were up-regulated by both cordycepin and adenosine.ConclusionBased on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.
BackgroundCordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs).MethodsDendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis.ResultsCME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot.ConclusionThese results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.
Dioscoreae rhizome (DR) has been used in traditional medicine to treat numerous diseases and reported to have anti-diabetes and antitumor activities. The pharmacological and biochemical mechanisms of the water extracts of DR (EDR) on macrophages in immune responses have not been clearly elucidated. We examined whether EDR suppresses the production of pro-inflammatory cytokines and the expression of co-stimulatory molecules. EDR reduced the production of NO and PGE2 through the suppressed gene and protein expression of iNOS and COX-2 in the both RAW 264.7 cells and peritoneal macrophages. The production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 production were suppressed by EDR. The change of gene expression by EDR treatment was analyzed by using RT-PCR, and the associated mRNA expression was inhibited same as cytokine production. Western blot analysis showed the augmentation of cytokine related protein on EDR treatment whereas anti-inflammatory cytokines, IL-4 and IL-10, did not significantly change. The expression level of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 also was reduced with the increment of EDR concentration. The nuclear translocation of NF-κB activity in LPS-activated macrophages was suppressed by EDR. These results showed EDR decreased pro-inflammatory cytokines via the inhibition of NF-κB dependent inflammatory protein level and suggesting that how EDR could be useful immunomodulatory agent for treating immunological diseases.
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