Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages

TLDR: It is shown 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-1 β as well as Nlrp3 inflammasome components via suppressing specific signal transduction pathways.

About: This article is published in Molecular Immunology.The article was published on 2013-12-31 and is currently open access. It has received 134 citations till now. The article focuses on the topics: Aloe vera & Cytokine secretion.

Figures

Fig. 1. Determination of cell viability. PMA-differentiated THP-1 macrophages (A) and primary human monocyte-derived macrophages (MF) (B) were treated with increasing concentration of solvent or Aloe vera. Results were obtained from three

Fig. 4. Effect of Aloe vera on LPS-induced expression of NLRP3 and procaspase-1. Primary human monocyte-derived macrophages were pretreated with the indicated amounts of Aloe vera for 1 h, then cells were activated with LPS. After 24 h, RNA was purified from cells and transcription of Nlrp3 (A) and procaspase-1 (C) was determined by quantitative RT-PCR. Gene expression is shown as the ratio of the studied transcripts relative to human cyclophilin expression (±SD) measured in triplicate (*p < 0.1, **p < 0.01). The protein levels of Nlrp3 (B) and procaspase-1 (D) were determined from whole cell lysate using Western blot method. To verify the loading of equal amount of protein s tomet W hown

Fig. 2. Effect of Aloe vera on LPS-induced cytokine production in THP-1 and primary human monocyte-derived macrophages. PMA-differentiated THP-1 cells were pretreated with 10 v/v% Aloe vera for 1 h then they were subsequently treated with LPS for 24 h (left panels). Primary human monocyte-derived macrophages (MF) were pretreated with 1 v/v% or 3 v/v% Aloe vera for 1 h then cells were incubated with LPS for 24 h (right panels). The supernatants were collected and production of IL-8, TNF , IL-6 and IL-1 cytokines were measured using an ELISA method in triplicate. Experiments were performed three times and a representative result set is shown. Mean ± SD values are provided as *p < 0.05, **p < 0.005, ***p < 0.0005.

Fig. 5. Aloe vera abolishes LPS-mediated enhancement of P2X7R expression. Primary human monocyte-derived macrophages were pretreated with the indicated amounts of Aloe vera for 1 h, then cells were activated with LPS for 24 h. RNA was purified from cells and transcription of P2X7R was determined by quantitative real-time PCR (A). Gene expression is shown as the ratio of the studied transcript relative to that of human cyclophilin (±SD) measured in triplicates. The protein expression of P2X7R was detected from whole cell lysate using Western blot technique (B). To verify the loading of equal amount of protein sample, -actin expression was determined. Western blots were quantified by densitometry. Results obtained from three independent experiments and one representative Western blot are shown. Mean ± SD values of three independent e

Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "Aloe vera downregulates lps-induced inflammatory cytokine production and expression of nlrp3 inflammasome in human macrophages" ?

However, its role on the IL-1 inflammatory cytokine production has not been studied. In this study the authors aimed to determine the effect of Aloe vera on the molecular mechanisms of Nlrp3 inflammasome-mediated IL-1 production in LPS-activated human THP-1 cells and monocyte-derived macrophages. Altogether, the authors show for the first time that Aloe vera-mediated strong reduction of IL-1 appears to be the consequence of the reduced expression of both pro-IL-1 as well as Nlrp3 inflammasome components via suppressing specific signal transduction pathways. Furthermore, the authors show that the expression of the ATP sensor P2X7 receptor is also downregulated by Aloe vera that could also contribute to the attenuated IL-1 cytokine secretion. Furthermore, LPS-induced activation of signaling pathways like NFB, p38, JNK and ERK were inhibited by Aloe vera in these cells. 

Q2. What is the role of IL-1 in macrophages?

Since P2X7 eceptor in macrophages is required for proper Nlrp3 inflammaome activation and for the production of mature, secreted IL-1 , loe-mediated changes in the expression of the ATP-sensor may lso contribute to its anti-inflammatory effect. 

Q3. What is the role of IL-1 in the development of human macrophages?

IL-1 together with TNF are mong the most powerful cytokines that under pathological conitions could cause cell degeneration and cell death resulting in ultiple organ dysfunction (Tracey et al., 1987). 

Q4. What is the role of aloe vera in inflammatory responses?

Aloe vera significantly decreases cytokine production of PS-activated macrophagesLPS is a TLR4 specific agonist that has been described to be strong inducer of inflammatory responses in macrophages. 

Q5. What is the effect of aloe vera on the signaling pathways?

Aloe vera inhibits the LPS-induced activation of NF- B, p38, JNK and ERK signal transduction pathwaysLPS induces a network of signaling pathways that, as a consequence, influence the expression of several genes. 

Q6. What is the role of IL-1 in the cell cycle?

It requires a “priming” stimulus that induce the expression of pro-IL-1 and that of the inflammasome components; furthermore, it requires stimuli that lead to the assembly and activation of inflammasome complex and ultimately to the cleavage of pro-IL-1 to its active IL-1 form (Vazquez et al., 1996; Bauernfeind et al., 2009). 

Q7. What is the effect of aloe vera on macrophages?

Their results show that Aloe vera treatment significantly down-regulated LPS-induced IL-8, TNF , IL-6, and IL-1 inflammatory cytokine production in a concentration dependent manner in both THP-1 cells and primary macrophages. 

Q8. How much aloe vera did not affect cell viability of primary MFs?

their results lso demonstrated that while in the case of MFs the highest nonoxic concentration of Aloe vera (3 v/v%) resulted in more than 0% reduction in cytokine production, the attenuation of cytokine roduction was less pronounced in THP-1 cells even with the 0 v/v% 

Q9. what is the effect of aloe vera gel on oxidative metabolism?

Effects of low molecular constituents from Aloe veragel on oxidative metabolism and cytotoxic and bactericidal activities of human neutrophils. 

Q10. What is the effect of aloe vera on the NF-B pathway?

In this study the authors sed stabilized Aloe vera gel supernatant as a clear, well-defined olution to examine its effect on the expression of inflammatory ytokines and that of the components of Nlrp3 inflammasome n LPS-activated macrophages. 

Q11. What is the effect of aloe vera on primary macrophages?

It should be noted, that not only the cytotoxic sensitivity of primary macrophages was higher than that of THP-1 cells, but also the susceptibility toward Aloe-mediated down-regulation was more pronounced in these cells. 

Q12. How much of the IL-1 expression in the THP-1 cells was significantly reduced?

The dramatically induced transcription of pro-IL-1 in the LPS-treated THP-1 cells was also significantly reduced in the presence of 10 v/v% 

Q13. What is the effect of aloe vera on the inflammatory response in rat co?

Antiinflammatory effects of Aloe vera on leukocyte-endothelium interaction in the gastric microcirculation of Helicobacter pylori-infected rats.