Immune Netw.  2012 Oct;12(5):213-216. 10.4110/in.2012.12.5.213.

Polyacetylene Compound from Cirsium japonicum var. ussuriense Inhibited Caspase-1-mediated IL-1beta Expression

• Shim H
• Moon JS
• Lee S
• Yim D
• Kang TJ

• KMID: 2150751
• DOI: http://doi.org/10.4110/in.2012.12.5.213

Abstract

Our previous report showed that polyacetylene compound, 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA) from the root of Cirsium japonicum var. ussuriense has anti-inflammatory activity. In this study we investigated the role of the PA as inhibitor of caspase-1, which converts prointerleukin-1beta (proIL-1beta) to active IL-1beta and is activated by inflammasome involved in the inflammatory process. We tested the effect of PA on the production of pro-inflammatory cytokines, IL-1beta in murine macrophage cell line, RAW264.7. PA inhibited lipopolysaccharide (LPS)-induced IL-1beta production by macrophages at a dose dependent manner. PA also suppressed the activation of caspase-1. The mRNA level of ASC (apoptosis-associated spec-like protein containing a CARD), an important adaptor protein of inflammasome, was decreased in the PA treated group. Therefore our results suggest that the anti-inflammatory effect of PA is due to inhibit the caspase-1 activation.

Keyword

Polyacetylene compound; Anti-inflammatory activity; Caspase-1; Inflammasome; Cirsium japonicum

MeSH Terms

Cell Line
Cirsium
Cytokines
Macrophages
Polyacetylenes
RNA, Messenger
Cytokines
Polyacetylenes
RNA, Messenger

Figure

• 

  Figure 1 IL-1β production and caspase-1 activation by LPS were inhibited with treatment of PA in RAW 264.7 cells. (A, B) RAW264.7 cells were plated on 12 well cell culture plate, treated with PA (A, B) at a dose dependent manner (12.5~100 µg/ml). (C, D) In some experiments, the cells were treated with PA (50 µg/ml) or caspase-1 inhibitor, Ac-YVAD-CMK (C, D, 20 uM) for 1 hr, and then with LPS (100 ng/ml). After 24 h of these treatments, cell culture supernatants and cell lysates were collected and assayed for IL-1b secretion and caspase-1 activity, respectively. The data are representative of at least three independent experiments, each done in triplicate; *p<0.05, **p<0.01 compared to control groups treated with LPS alone.

• 

  Figure 2 The expression of genes (A: caspase-1; B: ASC) involved in the inflammasome in RAW 264.7 cells treated with PA (50 µg/ml) and LPS (100 ng/ml) by Real-time PCR. The data are representative of at least three independent experiments, each done in triplicate; *p<0.05 compared to control groups treated with LPS alone.

Reference

1. Philpott DJ, Girardin SE. The role of Toll-like receptors and Nod proteins in bacterial infection. Mol Immunol. 2004. 41:1099–1108.

2. Franchi L, Park JH, Shaw MH, Marina-Garcia N, Chen G, Kim YG, Núñez G. Intracellular NOD-like receptors in innate immunity, infection and disease. Cell Microbiol. 2008. 10:1–8.

3. Kanneganti TD, Lamkanfi M, Núñez G. Intracellular NOD-like receptors in host defense and disease. Immunity. 2007. 27:549–559.

4. Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS, Flavell RA. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science. 1995. 267:2000–2003.

5. Mariathasan S, Monack DM. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol. 2007. 7:31–40.

6. Kang TJ, Moon JS, Yim DS, Lee SK. Polyacetylene compound from Cirsium japonicum var. ussuriense inhibits the LPS-induced inflammatory reaction via suppression of NF-κB activity in RAW 264.7 cells. Biomol Ther. 2011. 19:97–101.

7. Kang TJ, Basu S, Zhang L, Thomas KE, Vogel SN, Baillie L, Cross AS. Bacillus anthracis spores and lethal toxin induce IL-1beta via functionally distinct signaling pathways. Eur J Immunol. 2008. 38:1574–1584.

8. Joshi VD, Kalvakolanu DV, Hebel JR, Hasday JD, Cross AS. Role of caspase 1 in murine antibacterial host defenses and lethal endotoxemia. Infect Immun. 2002. 70:6896–6903.

9. Nathan C. Points of control in inflammation. Nature. 2002. 420:846–852.

10. Rankin JA. Biological mediators of acute inflammation. AACN Clin Issues. 2004. 15:3–17.

11. Cho W, Park SJ, Shin JS, Noh YS, Cho EJ, Nam JH, Lee KT. Anti-inflammatory effects of the methanol extract of Polytrichum Commune via NF-κB inactivation in RAW 264.7 cells. Biomol Ther. 2008. 16:385–393.

12. Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose-Girma M, Erickson S, Dixit VM. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 2004. 430:213–218.

13. Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA, et al. Molecular cloning of the interleukin-1 beta converting enzyme. Science. 1992. 256:97–100.