[en] Staphylococcus (S.) aureus is a major udder pathogen causing bovine mastitis. Some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), enhance extracellular and intracellular growth of S. aureus, indicating that the inflammatory process favors S. aureus infection. Helenalin is a sesquiterpene lactone with potent anti-inflammatory properties. This study was designed to evaluate the effects of helenalin on S. aureus infection. First, in vitro experiments were conducted. These studies revealed that proliferation of S. aureus in bovine mammary epithelial MAC-T cells treated in the presence or absence of TNF-alpha was markedly reduced in the presence of helenalin. Secondly, in vivo effects of helenalin were investigated. Lactating mice treated in the presence or absence of helenalin were challenged by the intramammary route with S. aureus and the bacteria in the mammary glands were counted 12 h after infection. Significantly less numbers of bacteria were recovered from the infected glands of helenalin-treated mice compared with untreated mice. Moreover, histological examination of mammary tissue from helenalin-treated mice that were challenged with S. aureus indicated that helenalin is able to significantly reduce leukocyte infiltration in the mammary gland following S. aureus inoculation. Our results show that helenalin reduces S. aureus intracellular growth and experimental S. aureus infection. We conclude that helenalin may be of potential interest in the treatment of S. aureus-induced mastitis in the bovine species.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Boulanger, D.; Université de Liège - ULiège
Brouillette, E.; Université de Scherbrooke Canada
Jaspar, F.; Université de Liège - ULiège
Malouin, F.; université de Scherbrooke Canada
Mainil, Jacques ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires > Bactériologie et pathologie des maladies bactériennes
Bureau, Fabrice ✱; Université de Liège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Lekeux, Pierre ✱; Université de Liège > Département des sciences fonctionnelles (DSF) > Physiologie
✱ These authors have contributed equally to this work.
Language :
English
Title :
Helenalin reduces Staphylococcus aureus infection in vitro and in vivo
Almeida R.A., Matthews K.R., Cifrian E., Guidry A.J., and Oliver S.P. Staphylococcus aureus invasion of bovine mammary epithelial cells. J. Dairy Sci. 79 (1996) 1021-1026
Bork P.M., Schmitz M.L., Kuhnt M., Escher C., and Heinrich M. Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB. FEBS Lett. 402 (1997) 85-90
Brouillette E., Grondin G., Lefebvre C., Talbot B.G., and Malouin F. Mouse mastitis model of infection for antimicrobial compound efficacy studies against intracellular and extracellular forms of Staphylococcus aureus. Vet. Microbiol. 101 (2004) 253-262
Donnarumma G., Paoletti I., Buommino E., Tufano M.A., and Baroni A. Alpha-MSH reduces the internalization of Staphylococcus aureus and down-regulates HSP 70, integrins and cytokine expression in human keratinocyte cell lines. Exp. Dermatol. 13 (2004) 748-754
Ellington J.K., Elhofy A., Bost K.L., and Hudson M.C. Involvement of mitogen-activated protein kinase pathways in Staphylococcus aureus invasion of normal osteoblasts. Infect. Immun. 9 (2001) 5235-5242
Gertsch J., Sticher O., Schmidt T., and Heilmann J. Influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in Jurkat T cells and human peripheral blood cells: anti-inflammatory and cytotoxic effects. Biochem. Pharmacol. 66 (2003) 2141-2153
Hall I.H., Lee K.H., Starnes C.O., Sumida Y., Wu R.Y., Waddell T.G., Cochran J.W., and Gerhart K.G. Anti-inflammatory activity of sesquiterpene lactones and related compounds. J. Pharm. Sci. 68 (1979) 537-542
Hall I.H., Starnes C.O., Lee K.H., and Waddell T.G. Mode of action of sesquiterpene lactones as anti-inflammatory agents. J. Pharm. Sci. 69 (1980) 537-543
Hamill R.J., Vann J.M., and Proctor R.A. Phagocytosis of Staphylococcus aureus by cultured bovine aortic endothelial cells: model for postadherence events in endovascular infections. Infect. Immun. 54 (1986) 833-836
Hwang D., Fischer N.H., Jang B.C., Tak H., Kim J.K., and Lee W. Inhibition of the expression of inducible cyclooxygenase and pro-inflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases. Biochem. Biophys. Res. Commun. 226 (1996) 810-818
Hyunh H.T., Robitaille G., and Turner J.D. Establishment of bovine mammary epithelial cells (MAC-T): an in vivo model for bovine lactation. Exp. Cell Res. 197 (1991) 191-197
Jett B.D., and Gilmore M.S. Internalization of Staphylococcus aureus by human corneal epithelial cells: role of bacterial fibronectin-binding protein and host cell factors. Infect. Immun. 70 (2002) 4697-4700
Kahl B.C., Goulian M., van Wamel W., Herrmann M., Simon S.M., Kaplan G., Peters G., and Cheung A.L. Staphylococcus aureus RN6390 replicates and induces apoptosis in a pulmonary epithelial cell line. Infect. Immun. 68 (2000) 5385-5392
Kanangat S., Meduri G.U., Tolley E.A., Patterson D.R., Meduri C.U., Pak C., Griffin J.P., Bronze M.S., and Schaberg D.R. Effects of cytokines and endotoxin on the intracellular growth of bacteria. Infect. Immun. 67 (1999) 2834-2840
Kanangat S., Bronze M.S., Meduri G.U., Postlethwaite A., Stentz F., Tolley E., and Schaberg D. Enhanced extracellular growth of Staphylococcus aureus in the presence of selected linear peptide fragments of human interleukin (IL)-1beta and IL-1 receptor antagonist. J. Infect. Dis. 183 (2001) 65-69
Kang B.Y., Chung S.W., and Kim T.S. Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by parthenolide, a predominant sesquiterpene lactone in Tanacetum parthenium: involvement of nuclear factor-kappaB. Immunol. Lett. 77 (2001) 159-163
Liu S.F., Ye X., and Malik A.B. In vivo inhibition of nuclear factor-kappa B activation prevents inducible nitric oxide synthase expression and systemic hypotension in a rat model of septic shock. J. Immunol. 159 (1997) 3976-3983
Liu S.F., Ye X., and Malik A.B. Pyrrolidine dithiocarbamate prevents I-kappaB degradation and reduces microvascular injury induced by lipopolysaccharide in multiple organs. Mol. Pharmacol. 55 (1999) 658-667
Luo G., Niesel D.W., Shaban R.A., Grimm E.A., and Klimpel G.R. Tumor necrosis factor alpha binding to bacteria: evidence for a high-affinity receptor and alteration of bacterial virulence properties. Infect. Immun. 61 (1993) 830-835
Lyss G., Schmidt T.J., Merfort I., and Pahl H.L. Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB. Biol. Chem. 378 (1997) 951-961
Lyss G., Knorre A., Schmidt T.J., Pahl H.L., and Merfort I. The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65. J. Biol. Chem. 273 (1998) 33508-33516
Meduri G.U., Kanangat S., Stefan J., Tolley E., and Schaberg D. Cytokines IL-1beta, IL-6, and TNF-alpha enhance in vitro growth of bacteria. Am. J. Respir. Crit. Care Med. 160 (1999) 961-967
Meduri G.U., Kanangat S., Bronze M., Patterson D.R., Meduri C.U., Pak C., Tolley E.A., and Schaberg D.R. Effects of methylprednisolone on intracellular bacterial growth. Clin. Diagn. Lab. Immunol. 8 (2001) 1156-1163
Pahl H.L. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18 (1999) 6853-6866
Porat R., Clark B.D., Wolff S.M., and Dinarello C.A. Enhancement of growth of virulent strains of Escherichia coli by interleukin-1. Science 254 (1991) 430-432
Sheehan M., Wong H.R., Hake P.W., Malhotra V., O'Connor M., and Zingarelli B. Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxic shock in rodents. Mol. Pharmacol. 61 (2002) 953-963
Soell M., Diab M., Haan-Archipoff G., Beretz A., Herbelin C., Poutrel B., and Klein J.P. Capsular polysaccharide types 5 and 8 of Staphylococcus aureus bind specifically to human epithelial (KB) cells, endothelial cells, and monocytes and induce release of cytokines. Infect. Immun. 63 (1995) 1380-1386
Wang J.E., Jorgensen P.F., Almlof M., Thiemermann C., Foster S.J., Aasen A.O., and Solberg R. Peptidoglycan and lipoteichoic acid from Staphylococcus aureus induce tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-10 production in both T cells and monocytes in a human whole blood model. Infect. Immun. 68 (2000) 3965-3970
