Staphylococcus aureus regulates secretion of interleukin-6 and monocyte chemoattractant protein-1 through activation of nuclear factor kappaB signaling pathway in human osteoblasts

Ning, Rende; Zhang, Xianlong; Guo, Xiaokui; Li, Qingtian

doi:10.1016/S1413-8670(11)70173-8

Article information

Abstract

Objective

Activation of nuclear factor kappaB by diverse bacteria regulates the secretion of chemokines and cytokines. Staphylococcus aureus (S. aureus)-infected osteoblasts can significantly increase the secretion of interleukin-6 and monocyte chemoattractant protein-1. The aim of this study was to investigate whether S. aureus can activate nuclear factor kappaB in human osteoblasts, and whether the activation of nuclear factor kappaB by S. aureus regulates the secretion of interleukin-6 and monocyte chemoattractant protein-1.

Methods

Immunoblot and electrophoretic mobility shift assay were used to detect the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in response to S. aureus, respectively. Enzyme-linked immunosorbent assay was used to measure the secretion of interleukin-6 and monocyte chemoattractant protein-1 in the supernatants. Lastly, carbobenzoxyl-l-leucinyl-l-leucinyl-l-leucinal, an inhibitor of the nuclear factor kappaB, was used to determine if activation of nuclear factor kappaB by S. aureus in human osteoblasts regulates the secretions of interleukin-6 and monocyte chemoattractant protein-1.

Results

Our results for the first time demonstrated that S. aureus can induce the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in a time and dose-dependent manner. In addition, inhibition of nuclear factor kappaB by carbobenzoxyl-l-leucinyl-l-leucinyl-l-leucinal suppressed the secretion of interleukin-6 and monocyte chemoattractant protein-1 in the supernatants of S. aureus-infected human osteoblasts in a dose-dependent manner.

Conclusions

These findings suggest that S. aureus can activate nuclear factor kappaB in human osteoblasts, and subsequently regulate the secretion of interleukin-6 and monocyte chemoattractant protein-1. The nuclear factor kappaB transcription factor regulates a number of genes involved in a wide variety of biological processes. Further study of the effects of nuclear factor kappaB activation on S. aureus-infected human osteoblast may provide us new insights into discovery of the immune mechanisms in osteomyelitis.

Keywords:

Staphylococcus aureus

osteoblasts

NF-kappaB

interleukin-6

chemokine CCL2

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References

[1.]

L.S. Jorge, A.G. Chueire, A.R.B. Rossit, Osteomyelitis:.

a current challenge.

Braz J Infect Dis, 14 (2010), pp. 310-315

Medline

[2.]

D.P. Lew, F.A. Waldvogel.

Osteomyelitis.

Lancet, 364 (2004), pp. 369-379

http://dx.doi.org/10.1016/S0140-6736(04)16727-5 | Medline

[3.]

K.L. Bost, W.K. Ramp, N.C. Nicholson, et al.

Staphylococcus aureus infection of mouse or human osteoblasts induces high levels of interleukin-6 and interleukin-12 production.

J Infect Dis, 180 (1999), pp. 1912-1920

http://dx.doi.org/10.1086/315138 | Medline

[4.]

K.L. Bost, J.L. Bento, C.C. Petty, et al.

Monocyte chemoattractant protein-1 expression by osteoblasts following infection with Staphylococcus aureus or Salmonella.

J Interferon Cytokine Res, 21 (2001), pp. 297-304

http://dx.doi.org/10.1089/107999001300177484 | Medline

[5.]

I. Marriott.

Osteoblast responses to bacterial pathogens: a previously unappreciated role for bone-forming cells in host defense and disease progression.

Immunol Res, 30 (2004), pp. 291-308

http://dx.doi.org/10.1385/IR:30:3:291 | Medline

[6.]

K.M. Wright, J.S. Friedland.

Regulation of chemokine gene expression and secretion in Staphylococcus aureus-infected osteoblasts.

Microbes Infect, 6 (2004), pp. 844-852

http://dx.doi.org/10.1016/j.micinf.2004.04.008 | Medline

[7.]

M. Naumann, S. Wessler, C. Bartsch, et al.

Neisseria gonorrhoeae epithelial cell interaction leads to the activation of the transcription factors nuclear factor kappaB and activator protein 1 and the induction of inflammatory cytokines.

J Exp Med, 186 (1997), pp. 247-258

Medline

[8.]

R.J. Carmody, Y.H. Chen.

Nuclear factor-kappaB: activation and regulation during toll-like receptor signaling.

Cell Mol Immunol, 4 (2007), pp. 31-41

Medline

[9.]

A. Kriete, K.L. Mayo.

Atypical pathways of NF-kappaB activation and aging.

Exp Gerontol, 44 (2009), pp. 250-255

http://dx.doi.org/10.1016/j.exger.2008.12.005 | Medline

[10.]

A. Morotti, D. Cilloni, M. Pautasso, et al.

NF-kB inhibition as a strategy to enhance etoposide-induced apoptosis in K562 cell line.

Am J Hematol, 81 (2006), pp. 938-945

http://dx.doi.org/10.1002/ajh.20732 | Medline

[11.]

U. Panzer, O.M. Steinmetz, J.E. Turner, et al.

Resolution of renal inflammation: a new role for NF-kappaB1 (p50) in inflammatory kidney diseases.

Am J Physiol Renal Physiol, 297 (2009), pp. F429-F439

http://dx.doi.org/10.1152/ajprenal.90435.2008 | Medline

[12.]

T. Ohno, N. Okahashi, I. Morisaki, A. Amano.

Signaling pathways in osteoblast proinflammatory responses to infection by Porphyromonas gingivalis.

Oral Microbiol Immunol, 23 (2008), pp. 96-104

http://dx.doi.org/10.1111/j.1399-302X.2007.00393.x | Medline

[13.]

P.J. Tsai, Y.H. Chen, C.H. Hsueh, et al.

Streptococcus pyogenes induces epithelial inflammatory responses through NF-kappaB/MAPK signaling pathways.

Microbes Infect, 8 (2006), pp. 1440-1449

http://dx.doi.org/10.1016/j.micinf.2006.01.002 | Medline

[14.]

E. Medina, D. Anders, G.S. Chhatwal.

Induction of NF-kappaB nuclear translocation in human respiratory epithelial cells by group A streptococci.

Microb Pathog, 33 (2002), pp. 307-313

Medline

[15.]

P. Mendez-Samperio, A. Perez, L. Rivera.

Mycobacterium bovis Bacillus Calmette-Guerin (BCG)-induced activation of PI3K/Akt and NF-kB signaling pathways regulates expression of CXCL10 in epithelial cells.

Cell Immunol, 256 (2009), pp. 12-18

http://dx.doi.org/10.1016/j.cellimm.2008.12.002 | Medline

[16.]

N. Nishimoto, T. Kishimoto.

Inhibition of IL-6 for the treatment of inflammatory diseases.

Curr Opin Pharmacol, 4 (2004), pp. 386-391

http://dx.doi.org/10.1016/j.coph.2004.03.005 | Medline

[17.]

J. Van Snick.

Interleukin-6: an overview.

Annu Rev Immunol, 8 (1990), pp. 253-278

http://dx.doi.org/10.1146/annurev.iy.08.040190.001345 | Medline

[18.]

C. Pasare, R. Medzhitov.

Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.

Science, 299 (2003), pp. 1033-1036

http://dx.doi.org/10.1126/science.1078231 | Medline

[19.]

S.L. Deshmane, S. Kremlev, S. Amini, B.E. Sawaya.

Monocyte chemoattractant protein-1 (MCP-1): an overview.

J Interferon Cytokine Res, 29 (2009), pp. 313-326

http://dx.doi.org/10.1089/jir.2008.0027 | Medline

[20.]

A. Sakamoto, H. Ishibashi-Ueda, Y. Sugamoto, et al.

Expression and function of ephrin-B1 and its cognate receptor EphB2 in human atherosclerosis: from an aspect of chemotaxis.

Clin Sci (Lond), 114 (2008), pp. 643-650

[21.]

I. Marriott, D.L. Gray, S.L. Tranguch, et al.

Osteoblasts express the inflammatory cytokine interleukin-6 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue.

Am J Pathol, 164 (2004), pp. 1399-1406

http://dx.doi.org/10.1016/S0002-9440(10)63226-9 | Medline

[22.]

I. Marriott, D.L. Gray, D.M. Rati, et al.

Osteoblasts produce monocyte chemoattractant protein-1 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue.

Bone, 37 (2005), pp. 504-512

http://dx.doi.org/10.1016/j.bone.2005.05.011 | Medline

[23.]

S.N. Somayaji, S. Ritchie, M. Sahraei, et al.

Staphylococcus aureus induces expression of receptor activator of NF-kappaB ligand and prostaglandin E2 in infected murine osteoblasts.

Infect Immun, 76 (2008), pp. 5120-5126

http://dx.doi.org/10.1128/IAI.00228-08 | Medline

[24.]

J. Zhu, X. Zhang, C. Wang, X. Peng.

Periprosthetic strain magnitude- dependent upregulation of type I collagen synthesis in human osteoblasts through an ERK1/2 pathway.

Int Orthop, 33 (2009), pp. 1455-1460

http://dx.doi.org/10.1007/s00264-009-0735-z | Medline

[25.]

V.B. Andela, R.N. Rosier.

The proteosome inhibitor MG132 attenuates retinoic acid receptor trans-activation and enhances trans-repression of nuclear factor kappaB Potential relevance to chemo-preventive interventions with retinoids.

Mol Cancer, 3 (2004), pp. 8

http://dx.doi.org/10.1186/1476-4598-3-8 | Medline

[26.]

L. Fantuzzi, F. Spadaro, C. Purificato, et al.

Phosphatidylcholinespecific phospholipase C activation is required for CCR5-dependent NF-kB-driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages.

Blood, 111 (2008), pp. 3355-3363

http://dx.doi.org/10.1182/blood-2007-08-104901 | Medline

[27.]

D. Mitchell, C. Olive.

Regulation of Toll-like receptor-induced chemokine production in murine dendritic cells by mitogen activated protein kinases.

Mol Immunol, 47 (2010), pp. 2065-2073

http://dx.doi.org/10.1016/j.molimm.2010.04.004 | Medline

[28.]

S. Akira, S. Uematsu, O. Takeuchi.

Pathogen recognition and innate immunity.

Cell, 124 (2006), pp. 783-801

http://dx.doi.org/10.1016/j.cell.2006.02.015 | Medline

[29.]

I. Bekeredjian-Ding, S. Inamura, T. Giese, et al.

Staphylococcus aureus protein A triggers T cell-independent B cell proliferation by sensitizing B cells for TLR2 ligands.

J Immunol, 178 (2007), pp. 2803-2812

Medline

[30.]

M.C. Dessing, M. Schouten, C. Draing, et al.

Role played by Toll like receptors 2 and 4 in lipoteichoic acid-induced lung inflammation and coagulation.

J Infect Dis, 197 (2008), pp. 245-252

http://dx.doi.org/10.1086/524873 | Medline

[31.]

K. Miyake.

Innate recognition of lipopolysaccharide by Tolllike receptor 4-MD-2.

Trends Microbiol, 12 (2004), pp. 186-192

http://dx.doi.org/10.1016/j.tim.2004.02.009 | Medline

[32.]

O. Takeuchi, S. Akira.

MyD88 as a bottle neck in Toll/IL-1 signaling.

Curr Top Microbiol Immunol, 270 (2002), pp. 155-167

Medline

[33.]

T. Kikuchi, T. Matsuguchi, N. Tsuboi, et al.

Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors.

J Immunol, 166 (2001), pp. 3574-3579

Medline

[34.]

D. Varoga, C.J. Wruck, M. Tohidnezhad, et al.

Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3.

Histochem Cell Biol, 131 (2009), pp. 207-218

http://dx.doi.org/10.1007/s00418-008-0522-8 | Medline

[35.]

N.A. Gasper, C.C. Petty, L.W. Schrum, et al.

Bacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4.

Infect Immun, 70 (2002), pp. 4075-4082

Medline

[36.]

D.R. Madrazo, S.L. Tranguch, I. Marriott.

Signaling via Toll-like receptor 5 can initiate inflammatory mediator production by murine osteoblasts.

Infect Immun, 71 (2003), pp. 5418-5421

Medline

[37.]

W. Zou, A. Amcheslavsky, Z. Bar-Shavit.

CpG oligodeoxynucleotides modulate the osteoclastogenic activity of osteoblasts via Toll-like receptor 9.

J Biol Chem, 278 (2003), pp. 16732-16740

http://dx.doi.org/10.1074/jbc.M212473200 | Medline

[38.]

H.C. Liou.

Regulation of the immune system by NF-kappaB and IkappaB.

J Biochem Mol Biol, 35 (2002), pp. 537-546

Medline

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