Eun-Young Kwon; Chulmin Park; Jae-Cheol Kwon; Si-Hyun Kim; Sun Hee Park; Su-Mi Choi; Dong-Gun Lee; Jin-Hong Yoo; Jung-Hyun Choi

doi:10.3947/ic.2010.42.5.291

Journal List > Infect Chemother > v.42(5) > 1035028

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Kwon, Park, Kwon, Kim, Park, Choi, Lee, Yoo, and Choi: Effects of Peroxisome Proliferator-Activated Receptor-γ on the Production of Tumor Necrosis Factor-α in Stimulated Human Monocoytes

Original Article

Infection & Chemotherapy

Infection & Chemotherapy 2010; 42(5): 291-295.

Published online: 31 October 2010

DOI: https://doi.org/10.3947/ic.2010.42.5.291

Effects of Peroxisome Proliferator-Activated Receptor-γ on the Production of Tumor Necrosis Factor-α in Stimulated Human Monocoytes

Eun-Young Kwon¹, Chulmin Park¹, Jae-Cheol Kwon², Si-Hyun Kim², Sun Hee Park², Su-Mi Choi², Dong-Gun Lee², Jin-Hong Yoo², Jung-Hyun Choi²

¹Catholic Research Institutes of Medical Science, College of Medicine, Catholic University of Korea, Seoul, Korea.

²Department of Internal Medicine, Division of Infectious Diseases, College of Medicine, Catholic University of Korea, Seoul, Korea.

Correspondence to Jung-Hyun Choi, M.D. Department of Internal Medicine, Division of Infectious Diseases, Incheon St. Mary's Hospital, Medical College of Medicine, Catholic University of Korea, 665 Bupyung 6-dong, Bupyung-gu, Incheon 403-720, Korea. Tel: +82-32-510-5666, Fax: +82-32-510-5683, cmcjh@catholic.ac.kr

Received 19 July 2010 Revised 3 September 2010 Accepted 3 September 2010

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

We evaluated the effects of peroxisome proliferator-activated receptor-γ (PPAR-γ) on the production of tumor necrosis factor-α (TNF-α) and expression of nuclear factor-κB (NF-κB) in stimulated THP-1 cells, a human monocyte cell line.

Materials and Methods

We evaluated the cytotoxic effect of 15-Deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂), one of natural PPAR-γ ligands, using commercial cell proliferation assay. Cells were pretreated with 15d-PGJ₂ and then stimulated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). The amount of TNF-α was measured by using commercial ELISA method. NF-κB activation was evaluated by Western blot analysis.

Results

15d-PGJ₂ showed dose-dependent cytotoxic effect on the tested cells after 4 hr of treatment. Stimulation of cells by LPS or LTA induced TNF-α production. TNF-α production was markedly decreased in the cells pretreated with 15d-PGJ₂ compared to cells treated only with LPS or LTA in a dose-dependent manner. Pretreatment of 15d-PGJ₂ reduced LPS or LTA induced NF-κB expression in the nuclear extracts of THP-1 cells.

Conclusion

15d-PGJ₂ pretreatment decreased TNF-α production from the THP-1 cells stimulated by LPS or LTA, and this assumed to be associated with inhibition of NF-κB activation.

Keywords: Peroxisome proliferator-activated receptor-γ (PPAR-γ), Tumor necrosis factor (TNF)-α, Nuclear factor-κB (NF-κB)

Figures and Tables

Figure 1

Effects of different concentrations of 15d-PGJ₂ on the cell viability in THP-1 cells (1×10⁴). Cell viability was assessed by WST-1 assay as described in the Materials and Methods section. Data are expressed as inhibition percentage compared to the untreated cells.

Figure 2

Effects of 15d-PGJ₂ on TNF-α production in THP-1 cells. TNF-α production of THP-1 cells were detected by ELISA method. Cells (1×10⁶ cells) were stimulated with LPS (100 ng/mL) (A) or LTA (1 µg/mL) (B) for 4 hr. 15d-PGJ₂ was added 4 hr before stimulation. Con, control; LPS, lipopolysaccharide; LTA; lipoteichoic acid (^aP<0.001 compared with control; ^bP<0.05, ^cP<0.001 compared with LPS or LTA stimulated cells).

Figure 3

Effects of 15d-PGJ₂ on NF-κB activity in THP-1 cells. Activity of NF-κB in nuclear extracts of THP-1 cells were detected by Western blot analysis. Cells (7×10⁶ cells) were stimulated with LPS (100 ng/mL) (A) or LTA (1 µg/mL) (B) for 2 hr. 15d-PGJ₂ was added 4 hr before stimulation. Con, control; LPS, lipopolysaccharide; LTA; lipoteichoic acid; GAPDH, glyceraldehydes-3-phsphate dehydrogenase.

References

1. Choi JH. Recent evidences of sepsis treatment. Infect Chemother. 2008. 40:67–75.

2. von Knethen A, Soller M, Brüne B. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and sepsis. Arch Immunol Ther Exp (Warsz). 2007. 55:19–25.

3. Ferré P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes. 2004. 53:Suppl 1. S43–S50.

4. Semple RK, Chatterjee VK, O'Rahilly S. PPAR gamma and human metabolic disease. J Clin Invest. 2006. 116:581–589.

5. Tsubouchi Y, Sano H, Kawahito Y, Mukai S, Yamada R, Kohno M, Inoue K, Hla T, Kondo M. Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis. Biochem Biophys Res Commun. 2000. 270:400–405.

6. Balakumar P, Rose M, Singh M. PPAR ligands: are they potential agents for cardiovascular disorders? Pharmacology. 2007. 80:1–10.

7. Soller M, Tautenhahn A, Brüne B, Zacharowski K, John S, Link H, von Knethen A. Peroxisome proliferator-activated receptor gamma contributes to T lymphocyte apoptosis during sepsis. J Leukoc Biol. 2006. 79:235–243.

8. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998. 391:82–86.

9. Chima RS, Hake PW, Piraino G, Mangeshkar P, Denenberg A, Zingarelli B. Ciglitazone ameliorates lung inflammation by modulating the inhibitor kappaB protein kinase/nuclear factor-kappaB pathway after hemorrhagic shock. Crit Care Med. 2008. 36:2849–2857.

10. Lee CH, Olson P, Evans RM. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology. 2003. 144:2201–2207.

11. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000. 14:1293–1307.

12. Zingarelli B, Cook JA. Peroxisome proliferator-activated receptor-gamma is a new therapeutic target in sepsis and inflammation. Shock. 2005. 23:393–399.

13. Han SY, Kim CH, Han KH, Cha DR, Kim HS. Combination treatment with retinoid and peroxisome proliferator-activated receptors (PPAR)-gamma agonist on streptozotocin-Induced diabetic nephropathy. Korean J Nephrol. 2007. 26:526–533.

14. Liu D, Zeng BX, Zhang SH, Wang YL, Zeng L, Geng ZL, Zhang SF. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, reduces acute lung injury in endotoxemic rats. Crit Care Med. 2005. 33:2309–2316.

15. Haraguchi G, Kosuge H, Maejima Y, Suzuki J, Imai T, Yoshida M, Isobe M. Pioglitazone reduces systematic inflammation and improves mortality in apolipoprotein E knockout mice with sepsis. Intensive Care Med. 2008. 34:1304–1312.

16. Boggild AK, Krudsood S, Patel SN, Serghides L, Tangpukdee N, Katz K, Wilairatana P, Liles WC, Looareesuwan S, Kain KC. Use of peroxisome proliferator-activated receptor gamma agonists as adjunctive treatment for Plasmodium falciparum malaria: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2009. 49:841–849.

17. Reddy RC, Narala VR, Keshamouni VG, Milam JE, Newstead MW, Standiford TJ. Sepsis-induced inhibition of neutrophil chemotaxis is mediated by activation of peroxisome proliferator-activated receptor-gamma. Blood. 2008. 112:4250–4258.

18. Chen YC, Shen SC, Tsai SH. Prostaglandin D(2) and J(2) induce apoptosis in human leukemia cells via activation of the caspase 3 cascade and production of reactive oxygen species. Biochim Biophys Acta. 2005. 1743:291–304.

19. Kim YA, Kim JH, Jung SJ, Gil JH, Ku NS, Park YS, Kim MS, Kim YK, Shin SY, Yoon HJ, Choi JY, Song YG, Kim JM. Effect of peroxisome proliferator-activated receptor gamma agonist on the incidence of sepsis in diabetic patients. Korean J Med. 2005. 69:Suppl 1. S168.

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