Aloe vera has been used in traditional herbal medicine as an immunomodulatory agent inducing anti-inflammatory effects. However, its role on the IL-1β inflammatory cytokine production has not been studied. IL-1β production is strictly regulated both at transcriptional and posttranslational levels through the activity of Nlrp3 inflammasome. In this study we aimed to determine the effect of Aloe vera on the molecular mechanisms of Nlrp3 inflammasome-mediated IL-1β production in LPS-activated human THP-1 cells and monocyte-derived macrophages. Our results show that Aloe vera significantly reduced IL-8, TNFα, IL-6 and IL-1β cytokine production in a dose dependent manner. The inhibitory effect was substantially more pronounced in the primary cells. We found that Aloe vera inhibited the expression of pro-IL-1β, Nlrp3, caspase-1 as well as that of the P2X7 receptor in the LPS-induced primary macrophages. Furthermore, LPS-induced activation of signaling pathways like NF-κB, p38, JNK and ERK were inhibited by Aloe vera in these cells. Altogether, we show for the first time that Aloe vera-mediated strong reduction of IL-1β appears to be the consequence of the reduced expression of both pro-IL-1β as well as Nlrp3 inflammasome components via suppressing specific signal transduction pathways. Furthermore, we show that the expression of the ATP sensor P2X7 receptor is also downregulated by Aloe vera that could also contribute to the attenuated IL-1β cytokine secretion. These results may provide a new therapeutic approach to regulate inflammasome-mediated responses.
Keywords: ASC; ATP; Aloe vera; Cytokine; ELISA; ERK; GM-CSF; IL-1β; IL-6; IL-8; IkBα; JNK; LPS; MAPK; MF; MMP-9; Macrophage; Matrix metallopeptidase 9; NF-κB; NLRP3; NOD-like receptor family pyrin domain-containing 3; Nlrp3 inflammasome; P2X purinergic receptor 7; P2X7R; PMA; RT-PCR; Signal transduction; THP-1; TLR4; TNFα; Toll-like receptor 4; adenosine-5′-triphosphate; apoptosis-associated speck-like protein containing a caspase recruitment domain; c-Jun N-terminal kinase; enzyme-linked immunosorbent assay; extracellular-signal-regulated kinase; granulocyte-macrophage colony stimulating factor; human acute monocytic leukemia cell line; interleukin-1β; interleukin-6; interleukin-8; lipopolysaccharide; macrophage; mitogen-activated protein kinase; nuclear factor kappa-light-chain-enhancer of activated B cells; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; phorbol myristate acetate; real-time polymerase chain reaction; tumor necrosis factor-alpha.
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