Suppressive Effect of Tomentosin on the Production of Inflammatory Mediators in RAW264.7 Cells

Park, Hyo-Hyun; Kim, Sun-Gun; Kim, Mi Jin; Lee, Ji‐Ean; Choi, Bong‐Keun; Jin, Meihua; Lee, Eunkyung

doi:10.1248/bpb.b14-00050

Cited by 29 publications

(20 citation statements)

References 23 publications

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“…Given the significant role of inflammation in the formation of acne vulgaris, we next tested the anti‐inflammatory activity of C16‐KWKW by measuring its inhibition of the expression of pro‐inflammatory cytokines produced by mouse macrophage RAW264.7 cells (Park et al, ). As observed previously, the inflammation associated with acne is possibly triggered by sebaceous lipids (Zouboulis et al, ; Zouboulis, Jourdan, & Picardo, ) or P. acnes (Nagy et al, ); thus, in this study, the production of cytokine was induced respectively by LPS and heat‐killed P. acnes .…”

Section: Resultsmentioning

confidence: 99%

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

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Background and Purpose Propionibacterium acnes is a Gram‐positive bacterium associated with the skin disorder acne. In this study, as fatty acids are considered to be important in the life habitat of P. acnes, we tested our lipopeptide library in an attempt to create potent P. acnes‐specific antimicrobial agents. Experimental Approach The antimicrobial activity of various lipopeptides was determined by measuring their minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore their mode of action. RAW264.7 cells stimulated with LPS and P. acnes respectively were used to measure their anti‐inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti‐inflammatory effects of the peptides tested in vivo. Key Results The most potent candidate, C16‐KWKW, was observed to be more active against P. acnes than against other non‐targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16‐KWKW was observed to be through interference with the integrity of the bacterial membrane, thereby impairing membrane permeability and causing leakage of inner contents of bacterial cells. Furthermore, C16‐KWKW inhibited the expression of pro‐inflammatory cytokines, such as IL‐1β, TNF‐α, and inducible NOS stimulated by both LPS and P. acnes, thus showing potential anti‐inflammatory activity, which was further verified in the in vivo animal studies. Conclusions and Implications C16‐KWKW is a lipopeptide displaying both anti‐P. acnes and anti‐inflammatory effects in vitro and in vivo and shows potential as a treatment for acne vulgaris induced by P. acnes.

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Section: Resultsmentioning

confidence: 99%

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

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“…Given the significant role of inflammation in the formation of acne vulgaris, we next tested the anti-inflammatory activity of C16-KWKW by measuring its inhibition of the expression of pro-inflammatory cytokines produced by mouse macrophage RAW264.7 cells (Park et al, 2014). As shown previously, the inflammation associated with acne is possibly triggered by sebaceous lipids (Zouboulis et al, 2005;Zouboulis, Jourdan, & Picardo, 2014) or P. acnes (Nagy et al, 2006); thus, in this study, the production of cytokine was induced respectively by LPS and heat-killed P. acnes.…”

Section: R E T R a C T E Dmentioning

confidence: 99%

Retracted: Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with dual antibacterial and anti‐inflammatory action

Yang

Wang

et al. 2019

British J Pharmacology

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Background and Purpose: Propionibacterium acnes (P. acnes) is a Gram-positive bacterium associated with the skin disorder acne. In this study, we determined the importance of fatty acids in the life habitat of P. acnes; we tested our lipopeptide library in an attempt to create potent P. acnes-specific antimicrobial agents. Experimental Approach: Antimicrobial activity was determined by the minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore the mode of action. RAW264.7 cells respectively stimulated with LPS and P. acnes were used to measure the anti-inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti-inflammatory effects of the peptides tested in vivo. Key Results: The most potent candidate, C16-KWKW, was observed to be more active against P. acnes, with an MIC of 2 μg•ml −1 , than against other non-targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16-KWKW was observed to be through interference with the integrity of bacterial membrane, thereby impairing membrane permeability and causing leakage of the inner contents of bacterial cells. In addition, C16-KWKW inhibited the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α, and inducible NOS, stimulated by both LPS and P. acnes, thus showing potential anti-inflammatory activity, which was further assessed in animal studies in vivo. Conclusions and Implications: C16-KWKW is a lipopeptide displaying both anti-P. acnes and anti-inflammatory effects in vitro and in vivo, and exhibits potential as a treatment for acne vulgaris induced by P. acnes. 1 | INTRODUCTION Acne vulgaris is a chronic skin disorder that often develops on the face and upper trunk and is characterized by the formation of comedones, papules, nodules, pustules, and cysts (Aslam, Fleischer, & Feldman, 2015). In addition, the disease is always associated with an emotional and psychological impact, which can result in anxiety, reduced selfesteem, and depression or even thoughts of suicide (Tasoula et al., 2012). It affected more than 630 million people globally in 2015, thus being ranked as the eighth most common disease in the world (Disease, Injury, & Prevalence, 2016). Current research shows that several factors are involved in the development of this condition including an overgrowth of the skin commensal bacteria, obstruction of the follicle, excess production of sebum, and inflammation of the

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“…Tomentosin is a sesquiterpene lactone isolated from I. viscosa (L.) Aiton., which is largely used in Moroccan folk medicine for its interesting pharmacological activities, including anti-inflammatory [Hernandez et al, 2007], hypoglycaemic and hypolipidemic [Zeggwagh et al, 2006] antibacterial and antifungal [Maoz and Neeman, 1998] effects and in vitro antiproliferative activity on various human cancer cell lines [Talib and Mahasneh, 2010]. It was shown that tomentosin exerts anti-inflammatory activity through the inhibition of inflammatory mediators (NO, iNOS, PGE2, COX-2, TNF-a, and IL-6) by regulating NF-kB activation and phosphorylation of p38/JNK kinases in RAW 264.7 cells [Li et al, 2011;Park et al, 2014]. Tomentosin was reported to possess a fungistatic effect [Cafarchia et al, 2001] and anticancer effect [Rozenblat et al, 2008].…”

mentioning

confidence: 99%

Tomentosin Induces Telomere Shortening and Caspase‐Dependant Apoptosis in Cervical Cancer Cells

Merghoub

Btaouri

Benbacer

et al. 2016

J of Cellular Biochemistry

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Tomentosin, a natural sesquiterpene lactone purified from of Inula viscosa L., was investigated for its anti-proliferative, telomere shortening, and apoptotic effects on human cervical cancer HeLa and SiHa cell lines. Tomentosin was found to inhibit the growth of SiHa and HeLa cell lines in dose and time-dependent manner (IC values of 7.10 ± 0.78 μM and 5.87 ± 0.36 μM, respectively after 96 h of treatment). As evidenced by TTAGGG telomere length assay, tomentosin target specifically the telomeric overhang lengthening. This was confirmed by the evaluation of the cytotoxic effects of tomentosin in the foetal fibroblast Wi38 and JW10 cells which were derived from Wi38 and express hTERT, the telomerase catalytic subunit. We found that JW10 cells are 4.7-fold more sensitive to tomentosin which argues for telomere as its specific target. Furthermore, we found that tomentosin mediate this cytotoxic effect by inducing apoptosis and cell cycle arrest at G2/M phase. Morphological features of treated cells, as evidenced by Hoechst 33324 staining, revealed that the cytotoxic effect was due to induction of apoptosis. This was accompanied by pro-caspase-3 cleavage, an increase in caspase-3 activity and a cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, tomentosin induced a decrease in mitochondrial membrane potential (ΔΨm) and an increase in reactive oxygen species (ROS), accompanied by a decrease in Bcl-2 expression. This indicates that tomentosin-induced apoptosis may involve a mitochondria-mediated signaling pathway. This study provides the first evidence that tomentosin targets telomere machinery and induces apoptosis in cervical cancer cells. The molecular mechanism underlying tomentosin-induced apoptosis may involve a mitochondria-mediated signaling pathway. J. Cell. Biochem. 118: 1689-1698, 2017. © 2016 Wiley Periodicals, Inc.

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Suppressive Effect of Tomentosin on the Production of Inflammatory Mediators in RAW264.7 Cells

Cited by 29 publications

References 23 publications

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti‐inflammatory action

Retracted: Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with dual antibacterial and anti‐inflammatory action

Tomentosin Induces Telomere Shortening and Caspase‐Dependant Apoptosis in Cervical Cancer Cells

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