Anti-inflammatory Effects of Spermidine in Lipopolysaccharide-stimulated BV2 Microglial Cells

Overview

Journal J Biomed Sci

Publisher Biomed Central

Specialty Biology

Date 2012 Mar 22

PMID 22433014

Citations 62

Authors

Yung Hyun Choi

Hye Young Park

Affiliations

Soon will be listed here.

Abstract

Background: Spermidine, a naturally occurring polyamine, displays a wide variety of internal biological activities including cell growth and proliferation. However, the molecular mechanisms responsible for its anti-inflammatory activity have not yet been elucidated.

Methods: The anti-inflammatory properties of spermidine were studied using lipopolysaccharide (LPS)-stimulated murine BV2 microglia model. As inflammatory parameters, the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were evaluated. We also examined the spermidine's effect on the activity of nuclear factor-kappaB (NF-κB), and the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) pathways.

Results: Pretreatment with spermidine prior to LPS treatment significantly inhibited excessive production of NO and PGE2 in a dose-dependent manner, and was associated with down-regulation of expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Spermidine treatment also attenuated the production of pro-inflammatory cytokines, including IL-6 and TNF-α, by suppressing their mRNA expressions. The mechanism underlying spermidine-mediated attenuation of inflammation in BV2 cells appeared to involve the suppression of translocation of NF-κB p65 subunit into the nucleus, and the phosphorylation of Akt and MAPKs.

Conclusions: The results indicate that spermidine appears to inhibit inflammation stimulated by LPS by blocking the NF-κB, PI3K/Akt and MAPKs signaling pathways in microglia.

Citing Articles

Polyamines protect porcine sperm from lipopolysaccharide-induced mitochondrial dysfunction and apoptosis via casein kinase 2 activation.

Li R, Wu X, Chen J, Cheng J, Zhu Z, Guo M J Anim Sci. 2024; 103.

PMID: 39704338 PMC: 11773192. DOI: 10.1093/jas/skae383.

Clinical Evidence Regarding Spermidine-Hyaluronate Gel as a Novel Therapeutic Strategy in Vestibulodynia Management.

Murina F, Graziottin A, Toni N, Schettino M, Bello L, Marchi A Pharmaceutics. 2024; 16(11).

PMID: 39598571 PMC: 11597842. DOI: 10.3390/pharmaceutics16111448.

The Anti-Inflammatory Activities of Benzylideneacetophenone Derivatives in LPS Stimulated BV2 Microglia Cells and Mice.

Kim M, Kang S, Oh S Biomol Ther (Seoul). 2024; 33(1):106-116.

PMID: 39390761 PMC: 11704402. DOI: 10.4062/biomolther.2024.049.

Effect of Spermidine on Endothelial Function in Systemic Lupus Erythematosus Mice.

Kim H, Massett M Int J Mol Sci. 2024; 25(18).

PMID: 39337408 PMC: 11432455. DOI: 10.3390/ijms25189920.

Recommendations for nutritional supplements for dry eye disease: current advances.

Cong Y, Zhang Y, Han Y, Wu Y, Wang D, Zhang B Front Pharmacol. 2024; 15:1388787.

PMID: 38873421 PMC: 11169594. DOI: 10.3389/fphar.2024.1388787.

References

Park B, Lee S, Seo J, Rhee J, Park J, Kim Y . Protection of burn-induced skin injuries by the flavonoid kaempferol. BMB Rep. 2010; 43(1):46-51. DOI: 10.5483/bmbrep.2010.43.1.046. View

Kitada M, Igarashi K, Hirose S, Kitagawa H . Inhibition by polyamines of lipid peroxide formation in rat liver microsomes. Biochem Biophys Res Commun. 1979; 87(2):388-94. DOI: 10.1016/0006-291x(79)91808-4. View

Kawano T, Anrather J, Zhou P, Park L, Wang G, Frys K . Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity. Nat Med. 2006; 12(2):225-9. DOI: 10.1038/nm1362. View

Merentie M, Uimari A, Pietila M, Sinervirta R, Keinanen T, Vepsalainen J . Oxidative stress and inflammation in the pathogenesis of activated polyamine catabolism-induced acute pancreatitis. Amino Acids. 2007; 33(2):323-30. DOI: 10.1007/s00726-007-0522-3. View

Garden G, Moller T . Microglia biology in health and disease. J Neuroimmune Pharmacol. 2007; 1(2):127-37. DOI: 10.1007/s11481-006-9015-5. View

Hunter A . Molecular hurdles in polyfectin design and mechanistic background to polycation induced cytotoxicity. Adv Drug Deliv Rev. 2006; 58(14):1523-31. DOI: 10.1016/j.addr.2006.09.008. View

Sarkar F, Li Y, Wang Z, Kong D . NF-kappaB signaling pathway and its therapeutic implications in human diseases. Int Rev Immunol. 2008; 27(5):293-319. DOI: 10.1080/08830180802276179. View

Platonova G, Nazarova O, Tennikova T . Synthetic polycation: polynucleotide interactions determined using liquid chromatography with short monolithic columns. J Sep Sci. 2009; 32(15-16):2674-81. DOI: 10.1002/jssc.200900144. View

Larque E, Sabater-Molina M, Zamora S . Biological significance of dietary polyamines. Nutrition. 2006; 23(1):87-95. DOI: 10.1016/j.nut.2006.09.006. View

10.

Wirenfeldt M, Ladeby R, Dalmau I, Banati R, Finsen B . [Microglia--biology and relevance to disease]. Ugeskr Laeger. 2005; 167(33):3025-30. View

11.

OBrien K, Fitzgerald D, Naiken K, Alugupalli K, Rostami A, Gran B . Role of the innate immune system in autoimmune inflammatory demyelination. Curr Med Chem. 2008; 15(11):1105-15. DOI: 10.2174/092986708784221458. View

12.

Mankan A, Lawless M, Gray S, Kelleher D, McManus R . NF-kappaB regulation: the nuclear response. J Cell Mol Med. 2009; 13(4):631-43. PMC: 3822870. DOI: 10.1111/j.1582-4934.2009.00632.x. View

13.

Lee J, Jhun B, Oh Y, Lee J, Choe W, Baik H . Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neurosci Lett. 2005; 396(1):1-6. DOI: 10.1016/j.neulet.2005.11.004. View

14.

Kong Thoo Lin P, Dance A, Bestwick C, Milne L . The biological activities of new polyamine derivatives as potential therapeutic agents. Biochem Soc Trans. 2003; 31(2):407-10. DOI: 10.1042/bst0310407. View

15.

Bachrach U . Naturally occurring polyamines: interaction with macromolecules. Curr Protein Pept Sci. 2005; 6(6):559-66. DOI: 10.2174/138920305774933240. View

16.

St-Onge M, Flamand N, Biarc J, Picard S, Bouchard L, Dussault A . Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils. Biochim Biophys Acta. 2007; 1771(9):1235-45. PMC: 2891965. DOI: 10.1016/j.bbalip.2007.06.002. View

17.

Nam N . Naturally occurring NF-kappaB inhibitors. Mini Rev Med Chem. 2006; 6(8):945-51. DOI: 10.2174/138955706777934937. View

18.

Kitada M, Naito Y, Igarashi K, Hirose S, KANAKUBO Y, Kitagawa H . Possible mechanism of inhibition by polyamines of lipid peroxidation in rat liver microsomes. Res Commun Chem Pathol Pharmacol. 1981; 33(3):487-97. View

19.

Amor S, Puentes F, Baker D, van der Valk P . Inflammation in neurodegenerative diseases. Immunology. 2010; 129(2):154-69. PMC: 2814458. DOI: 10.1111/j.1365-2567.2009.03225.x. View

20.

Caivano M . Role of MAP kinase cascades in inducing arginine transporters and nitric oxide synthetase in RAW264 macrophages. FEBS Lett. 1998; 429(3):249-53. DOI: 10.1016/s0014-5793(98)00578-x. View