FLLL31, a derivative of curcumin, attenuates airway inflammation in a multi-allergen challenged mouse model

Cao, Shu; Jiang, Rentao; Liu, Ren Ping; Bai, Jinye; Hou, Qi

doi:10.1016/j.intimp.2014.04.020

Cited by 14 publications

(15 citation statements)

References 38 publications

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“…Moreover, FLLL31 significantly attenuated recruitment of inflammatory cells and mucus hypersecretion in DRA-challenged murine lung sections. Importantly, FLLL31 reduced the expression of IL-17 and Ly-6G/Gr-1 + cells in DRA-challenged murine lungs [51]. Meanwhile, we observed that FLLL31 reduced the expression of CD31 in the lung sections (Data not shown), which is consistent with the observations that IL-17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease in K14-IL-17A(ind/+) mice [18].…”

Section: Discussionsupporting

confidence: 89%

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Yuan

Zhang

Zhuang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Interleukin-17 (IL-17) is a major pro-inflammatory cytokine that initiates and maintains inflammation. However, the molecular mechanisms as to how IL-17 influences endothelial cells to promote neutrophil recruitment are not fully understood. Methods: Human endothelial cells (HMECs) were stimulated with IL-17, and investigated for proliferation, migration, and tubule formation activities. Transwell chemotaxis and adhesion assays were performed to assess neutrophil recruitment. Cytokine production was measured by Cytokine Array Chip and ELISA. Western blotting and immunofluorescent analysis were used to detect the phosphorylation and translocation of STAT3. Specific inhibitors, small interfering RNA, and phosphorylation mutants were used to confirm that IL-17 induced STAT3 activation via IL-17RA signaling. Results: Activation of HMECs with IL-17 induced STAT3 phosphorylation and nuclear translocation, which were associated with induction of GRO-α, GM-CSF and IL-8, and neutrophil recruitment. Phosphorylation of STAT3 was identified mainly at the tyrosine in position 705 (Y705), and the Y705F mutants attenuated IL-17-mediated STAT3 activation. Moreover, specific inhibitors, FLLL31, or siRNA silencing of STAT3 attenuated HMECs activation, resulting in inhibition of GRO-α, GM-CSF, IL-8 production, and neutrophil recruitment. Furthermore, phosphorylation of STAT3 was identified as downstream of IL-17RA signaling. Conclusions: IL-17 induced STAT3 activation as a necessary step in endothelial cell activation and neutrophil recruitment.

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Section: Discussionsupporting

confidence: 89%

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Yuan

Zhang

Zhuang

et al. 2015

Cell Physiol Biochem

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“…In addition, loss of the diketone group through formation of the pyrazolic ring ( Jadhav et al, 2015 ) eliminated the effect on acute cell behaviour. Furthermore, FLLL31 ( Yuan et al, 2014 ), which has two hydrogens on the central carbon replaced by methyl groups, and two extra methoxy groups, also showed a reduction in potency (5-fold). Lastly, two structurally distinct compounds, EF24 and UBS109, were investigated, with both compounds considered to be curcumin derivatives ( Vilekar et al, 2015 ; Yamaguchi et al, 2014 ), where EF24 showed enhanced activity (1.8-fold), and UBS109 showed reduced activity (11-fold), in this model.…”

Section: Resultsmentioning

confidence: 99%

Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum

Cocorocchio

Baldwin

Stewart

et al. 2018

Disease Models &Amp; Mechanisms

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Natural compounds often have complex molecular structures and unknown molecular targets. These characteristics make them difficult to analyse using a classical pharmacological approach. Curcumin, the main curcuminoid of turmeric, is a complex molecule possessing wide-ranging biological activities, cellular mechanisms and roles in potential therapeutic treatment, including Alzheimer's disease and cancer. Here, we investigate the physiological effects and molecular targets of curcumin in Dictyostelium discoideum. We show that curcumin exerts acute effects on cell behaviour, reduces cell growth and slows multicellular development. We employed a range of structurally related compounds to show the distinct role of different structural groups in curcumin's effects on cell behaviour, growth and development, highlighting active moieties in cell function, and showing that these cellular effects are unrelated to the well-known antioxidant activity of curcumin. Molecular mechanisms underlying the effect of curcumin and one synthetic analogue (EF24) were then investigated to identify a curcumin-resistant mutant lacking the protein phosphatase 2A regulatory subunit (PsrA) and an EF24-resistant mutant lacking the presenilin 1 orthologue (PsenB). Using in silico docking analysis, we then showed that curcumin might function through direct binding to a key regulatory region of PsrA. These findings reveal novel cellular and molecular mechanisms for the function of curcumin and related compounds.

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“…The amount of IL-6 and TNF-α in the supernatants of macrophages was measured using enzyme-linked immunosorbent assay (ELISA) kits (eBioscience, San Diego, CA, USA) as mentioned previously. 24 Briefly, 1 × 10 5 RAW264.7 cells were seeded in 96-well plates in DMEM medium supplemented with 5% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. After incubating at 37 o C for 2 h, cells were replaced with fresh medium and challenged with 100 ng/mL LPS for 24 h. Then, cells were treated with 1, 5 and 20 μM BA in the presence of LPS.…”

Section: Methodsmentioning

confidence: 99%

Baicalin attenuates lipopolysaccharide-induced pro-inflammatory cytokine expression in murine macrophage cell line RAW264.7 through miR-124-STAT3 axis

et al. 2018

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Baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi, has shown a wide range of anti-inflammatory, antioxidative, antiviral, and antitumor properties. However, the molecular mechanism of how baicalin exerts its effects, especially on inflammation regulation, has not been fully investigated. In this article, we report the effects of baicalin on the mouse macrophage cell line RAW264.7. Our results demonstrate that baicalin inhibits the production of inflammatory factors interleukin-6 and tumor necrosis factor-alpha upon lipopolysaccharide stimulation of macrophages. We observed that baicalin inhibits STAT3 activation through retarding its expression and phosphorylation. Interestingly, baicalin treatment promotes the elevation of miR-124 in lipopolysaccharide-treated macrophages. Overexpression of the miR-124 mimic in RAW264.7 reduced STAT3 expression and phosphorylation. Furthermore, inhibition of miR-124 attenuated the dysregulation of STAT3 and reduction of inflammatory factors upon baicalin treatment. Our results revealed the molecular mechanism that baicalin attenuates pro-inflammatory cytokine production through miR-124-STAT3 signaling pathway, suggesting that miR-124 is an important modulator in regulating anti-inflammation by baicalin in macrophages.

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FLLL31, a derivative of curcumin, attenuates airway inflammation in a multi-allergen challenged mouse model

Cited by 14 publications

References 38 publications

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum

Baicalin attenuates lipopolysaccharide-induced pro-inflammatory cytokine expression in murine macrophage cell line RAW264.7 through miR-124-STAT3 axis

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