A novel marine halophenol derivative attenuates lipopolysaccharide-induced inflammation in RAW264.7 cells via activating phosphoinositide 3-kinase/Akt pathway.

BACKGROUND: 2,4',5'-Trihydroxyl-5,2'-dibromo diphenylmethanone (LM49), a novel active halophenol derivative synthesized by our group from marine plants, exhibits strong anti-inflammatory activities. However, molecular machineries involved in its effect have not been fully identified. The study was aimed to investigate the anti-inflammatory effect of LM49 on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and its underlying mechanism. METHODS: RAW264.7 cells were treated with LPS (10 µg/mL) and then exposed to different concentrations of LM49 (i.e., 5, 10, and 15 µM) for 24 h. Cytokine release in culture medium of RAW264.7 cells was measured by enzyme-linked immunosorbent assay (ELISA). Phagocytic capacity (FITC-dextran uptake) was determined by flow cytometry. The protein level of phosphoinositide 3-kinase (PI3K), AKT and p-AKT was measured by western blot analysis. RESULTS: Our findings revealed that LM49 reduced the production and mRNA levels of cytokines related to inflammation such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α), and increased the level of IL-10, an anti-inflammatory cytokine. In addition, LM49 decreased the production of nitric oxide and reactive oxygen species. Moreover, flow cytometry showed that LM49 significantly enhanced the phagocytic capacity (FITC-dextran uptake) of macrophages. The effects of LM49 were significantly inhibited by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. In particular, LY294002 attenuated the phagocytic capacity of RAW264.7 cells induced by LM49 and prevented the effects on cytokines. CONCLUSION: These findings suggest that LM49 possesses anti-inflammatory activity on LPS-stimulated RAW264.7 cells, in which the PI3K/Akt pathway plays an essential role. LM49 may have clinical utility as an anti-inflammatory agent. In this study, we demonstrated that a halophenol derivative (LM49) could possess anti-inflammatory activity on LPS-stimulated RAW264.7 cells by reducing pro-inflammatory cytokines and enhancing the phagocytic capacity, in which the PI3K/Akt pathway plays an essential role. LM49 may have clinical utility as an anti-inflammatory agent.

Cadmium hyperaccumulation as an inexpensive metal armor against disease in Crofton weed.

Invasive plants readily invade metal-contaminated areas. The hyperaccumulation of toxic heavy metals is not an uncommon feature among plant species. Although several hypotheses were proposed to explain this phenomenon, it is currently unclear how hyperaccumulation may benefit plants. The invasive Crofton weed (Ageratina adenophora) is a known hyperaccumulator of chromium and lead. We previously found that the species can also hyperaccumulate cadmium. The role of phytoaccumulation in defense to pathogen attack is unclear. We inoculated A. adenophora plants with a common generalist pathogen (Rhizoctonia solani) to test its resistance under cadmium treatment. We found evidence that cadmium hyperaccumulation reduced pathogen infection in A. adenophora. Our findings indicate elemental defense is highly cost efficient for hyperaccumulators inhabiting metal-contaminated sites, where plants were only modestly affected by cadmium. The reduction in pathogen damage conferred by cadmium was relatively high, particularly under lower cadmium levels. However, the benefits at higher levels may be capped. Elemental defense may be a key mechanism for plant invasion into polluted sites, especially in regions with widespread industrial activity. Our study highlights the importance of testing different metal concentrations when testing plant resistance and the importance of considering enemy attack when selecting plants for phytoremediation.

5,2'-Dibromo-2,4,5-trihydroxydiphenylmethanone, a novel immunomodulator of T lymphocytes by regulating the CD4+ T cell subset balance via activating the mitogen-activated protein kinase pathway.

5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone (LM49) exerted therapeutic effects against rat acute pyelonephritis by regulating immune responses, especially affecting T lymphocytes. However, its underlying action mechanism remains unclear. T lymphocytes play an irreplaceable role in immune responses. Therefore, we sought to understand whether LM49 is an immunomodulator of T lymphocytes. The results showed that LM49 promoted T lymphocyte proliferation, increased the number of CD4+ T cells, and increased the CD4+/CD8+ T cell ratio. LM49 regulated the CD4+ T cell subset balance by increasing the production of CD4+IL-2+, CD4+IL-4+, and CD4+IL-10+, and reducing the production of CD4+IL-17+, without changing the production of interferon-γ. LM49 had a significant effect on the mRNA expression of the transcription factors T-bet, GATA3, Foxp3, and RORγt. Furthermore, LM49 raised the phospho (p)-extracellular signal-regulated protein kinase 1/2, p-p38, and p-c-Jun N-terminal kinase expression levels. T cell proliferation, and the production of CD4+IL-2+, CD4+IL-4+, and CD4+IL-10+ induced by LM49, were decreased by inhibitors of mitogen-activated protein kinases (MAPKs). These results revealed that LM49 possesses immunomodulatory activity on T lymphocytes, in which the MAPK pathway plays an essential role.

Different Growth Promoting Effects of Endophytic Bacteria on Invasive and Native Clonal Plants.

The role of the interactions between endophytes and alien plants has been unclear yet in plant invasion. We used a completely germ-free culture system to quantify the plant growth-promoting (PGP) effects of endophytic bacteria Bacillus sp. on aseptic seedlings of Wedelia trilobata and of its native clonal congener W. chinensis. The endophytic bacteria did not affect the growth of W. chinensis, but they significantly promoted the growth of W. trilobata. With the PGP effects of endophytic bacteria, relative change ratios of the clonal traits and the ramets' growth traits of W. trilobata were significantly greater than those of W. chinensis. Our results indicate that the growth-promoting effects of endophytes may differ between invasive and native clonal plants, and the endophytes of invasive plant may be host-specific to facilitate plant invasion.