Ginger-derived bioactive compounds attenuate the Toll-like receptor mediated responses of human dendritic cells.

Ginger has been used for thousands of years for the treatment of many illnesses, from nausea to migraines. Recently, an interest has grown in ginger compounds in the context of autoimmune and inflammatory diseases due to their significant anti-inflammatory effects. Nevertheless, the effects and mechanism of action of these phytochemicals in human immune cells, particularly in dendritic cells (DCs) are unclear. In the present study, we investigated the effects of 6-gingerol and 6-shogaol, the major compounds found in ginger rhizome, on the functionality of primary human monocyte-derived DCs (moDCs). Here we report for the first time that 6-gingerol and 6-shogaol dampen the immunogenicity of human DCs by inhibiting their activation, cytokine production and T cell stimulatory ability. In particular, the bioactive compounds of ginger dose-dependently inhibited the upregulation of activation markers, and the production of different cytokines in response to synthetic Toll-like receptor (TLR) ligands. Moreover, both compounds could significantly reduce the Escherichia coli-triggered cytokine production and T cell stimulatory capacity of moDCs. We also provide evidence that the ginger-derived compounds attenuate DC functionality via inhibiting the nuclear factor-κB (NF-kB), mitogen activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) signaling cascades. Further, 6-shogaol but not 6-gingerol activates the AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (NRF2) pathways that might contribute to its anti-inflammatory action. Altogether, our results indicate that ginger-derived phytochemicals exert their anti-inflammatory activities via multiple mechanisms and suggest that 6-shogaol is more potent in its ability to suppress DC functionality than 6-gingerol.

Interleukin 4 gene polymorphisms and the risk of tuberculosis: A meta-analysis.

BACKGROUND: Interleukin-4 (IL-4) is implicated in the progression of tuberculosis (TB); however, these results remain controversial. OBJECTIVES: This meta-analysis examined the relationship between IL and 4 polymorphisms (-589C/T, +4221C > A, and -33C/T) and the risk of TB. METHODS: A retrospective database analysis was conducted using the CNKI and PubMed databases. Using fixed- and random-effects models, we calculated the combined odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We identified 14 articles related to this topic, and theresultsshowed that the IL-4 -589C/T polymorphism didnotinfluencethe risk of TB. However,in subgroupanalyses we found that the IL-4 -589C/T polymorphism was associated with the risk of TB inCaucasians (recessive modelOR = 2.54, 95% CI = 1.30-4.96). In our study, the IL-4--33C/T polymorphism was not associated with the risk of TB. The IL-4 + 4221C > A polymorphism was associated with the risk of TB (recessive model: OR = 1.40, 95% CI = 1.07-1.83). CONCLUSION: This meta-analysis showed that the IL-4 -589C/T polymorphism was associated with TB risk in Caucasian populations, and the IL-4 + 4221C > A polymorphism is associated with TB risk.