Abstract
Osteoblasts are bone-forming mesenchymal cells, while macrophages are cells of hematopoietic origin responsible for innate immunity. Lipopolysaccharide (LPS) can induce tolerance in macrophages, whereas interferon (IFN)-γ can activate macrophages to produce cytokines, exert bactericidal effects, and present antigens. In this study, we examined such macrophagic phenotypes regulated by LPS and IFN-γ in murine osteoblasts. In both primary calvarial osteoblasts and osteoblastic MC3T3-E1 cells, LPS pretreatment resulted in reduced production of IL-6 in response to a subsequent LPS stimulation or to Salmonella infection, indicating the existence of LPS-induced tolerance in osteoblasts. Furthermore, IFN-γ treatment of MC3T3-E1 cells resulted in both enhanced IL-6 production in response to LPS and upregulation of major histocompatibility complex class II (MHC II). Following infection, Salmonella-containing vacuoles (SCVs) were formed in MC3T3-E1 cells, and IFN-γ pretreatment enhanced bactericidal effects on intracellular Salmonella. Taken together, these observations indicate that osteoblasts can exhibit a subset of phenotypes reminiscent of macrophages in the course of bacterial infection.
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DP Lew FA Waldvogel (2004) ArticleTitleOsteomyelitis Lancet 364 369–379 Occurrence Handle15276398 Occurrence Handle1:CAS:528:DC%2BD2cXmtVSktbc%3D Occurrence Handle10.1016/S0140-6736(04)16727-5
DP Lew FA Waldvogel (1997) ArticleTitleOsteomyelitis N Engl J Med 336 999–1007 Occurrence Handle9077380 Occurrence Handle1:STN:280:ByiB383jvVA%3D Occurrence Handle10.1056/NEJM199704033361406
AH al-SAlem HA Ahmed S Qaisaruddin A Al-Jam'a AM Elbashier I Al-Dabbous (1992) ArticleTitleOsteomyelitis and septic arthritis in sickle cell disease in the eastern province of Saudi Arabia Int Orthop 16 398–402 Occurrence Handle1473897 Occurrence Handle1:STN:280:ByyC3MvpsVA%3D Occurrence Handle10.1007/BF00189627
R Medzhitov (2001) ArticleTitleToll-like receptors and innate immunity Nat Rev Immunol 1 135–145 Occurrence Handle11905821 Occurrence Handle1:CAS:528:DC%2BD38XlvF2qu74%3D Occurrence Handle10.1038/35100529
MJ Wick HG Ljunggren (1999) ArticleTitleProcessing of bacterial antigens for peptide presentation on MHC class I molecules Immunol Rev 172 153–162 Occurrence Handle10631944 Occurrence Handle1:CAS:528:DC%2BD3cXkvVaksg%3D%3D Occurrence Handle10.1111/j.1600-065X.1999.tb01363.x
G Karsenty EF Wagner (2002) ArticleTitleReaching a genetic and molecular understanding of skeletal development Dev Cell 2 389–406 Occurrence Handle11970890 Occurrence Handle1:CAS:528:DC%2BD38Xjt1ersb4%3D Occurrence Handle10.1016/S1534-5807(02)00157-0
WS Simonet DL Lacey CR Dunstan M Kelley MS Chang R Luthy HQ Nguyen S Wooden L Bennett T Boone et al. (1997) ArticleTitleOsteoprotegerin: a novel secreted protein involved in the regulation of bone density Cell 89 309–319 Occurrence Handle9108485 Occurrence Handle1:CAS:528:DyaK2sXislCgtLc%3D Occurrence Handle10.1016/S0092-8674(00)80209-3
H Yasuda N Shima N Nakagawa SI Mochizuki K Yano N Fujise Y Sato M Goto K Yamaguchi M Kuriyama et al. (1998) ArticleTitleIdentity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro Endocrinology 139 1329–1337 Occurrence Handle9492069 Occurrence Handle10.1210/en.139.3.1329
S Kanzaki M Ito Y Takada K Ogawa K Matsuo (2006) ArticleTitleResorption of auditory ossicles and hearing loss in mice lacking osteoproegerin Bone (NY) 39 414–419 Occurrence Handle1:CAS:528:DC%2BD28Xls1ejtLY%3D
T Kikuchi T Matsuguchi N Tsuboi A Mitani S Tanaka M Matsuoka G Yamamoto T Hishikawa T Noguchi Y Yoshikai (2001) ArticleTitleGene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors J Immunol 166 3574–3579 Occurrence Handle11207318 Occurrence Handle1:CAS:528:DC%2BD3MXhs1Oisb4%3D
NA Gasper CC Petty LW Schrum I Marriott KL Bost (2002) ArticleTitleBacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4 Infect Immun 70 4075–4082 Occurrence Handle12117914 Occurrence Handle1:CAS:528:DC%2BD38XlsFCmsLc%3D Occurrence Handle10.1128/IAI.70.8.4075-4082.2002
KL Bost WK Ramp NC Nicholson JL Bento I Marriott MC Hudson (1999) ArticleTitleStaphylococcus aureus infection of mouse or human osteoblasts induces high levels of interleukin-6 and interleukin-12 production J Infect Dis 180 1912–1920 Occurrence Handle10558948 Occurrence Handle1:CAS:528:DC%2BD3cXivVSrtw%3D%3D Occurrence Handle10.1086/315138
GS Firestein (2003) ArticleTitleEvolving concepts of rheumatoid arthritis Nature (Lond) 423 356–361 Occurrence Handle1:CAS:528:DC%2BD3sXjs1ynu7c%3D Occurrence Handle10.1038/nature01661
H Takayanagi K Ogasawara S Hida T Chiba S Murata K Sato A Takaoka T Yokochi H Oda K Tanaka et al. (2000) ArticleTitleT-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-α Nature (Lond) 408 600–605 Occurrence Handle1:CAS:528:DC%2BD3cXovFajs7c%3D Occurrence Handle10.1038/35046102
KL Bost JL Bento JK Ellington I Marriott MC Hudson (2000) ArticleTitleInduction of colony-stimulating factor expression following Staphylococcus or Salmonella interaction with mouse or human osteoblasts Infect Immun 68 5075–5083 Occurrence Handle10948128 Occurrence Handle1:CAS:528:DC%2BD3cXmtVeks70%3D Occurrence Handle10.1128/IAI.68.9.5075-5083.2000
T Nishiwaki T Yamaguchi C Zhao H Amano DH Kurt P Bornstein Y Toyama K Matsuo (2006) ArticleTitleReduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1 J Bone Miner Res 21 596–604 Occurrence Handle16598380 Occurrence Handle1:CAS:528:DC%2BD28Xkt1Kqs70%3D Occurrence Handle10.1359/jbmr.051216
A Nagy M Gertsenstein K Vintersten R Behringer (2003) Manipulating the mouse embryo: A laboratory manual, 3rd ed Cold Spring Harbor Laboratory Press, Cold Spring Harbor New York 371–373
PA Gulig R Curtiss SuffixIII (1987) ArticleTitlePlasmid-associated virulence of Salmonella typhimurium Infect Immun 55 2891–2901 Occurrence Handle3316027 Occurrence Handle1:CAS:528:DyaL1cXhvFWmtg%3D%3D
K Suda N Udagawa N Sato M Takami K Itoh JT Woo N Takahashi K Nagai (2004) ArticleTitleSuppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation J Immunol 172 2504–2510 Occurrence Handle14764723 Occurrence Handle1:CAS:528:DC%2BD2cXpslWqsg%3D%3D
FJ Hughes LD Buttery MV Hukkanen A O'Donnell J Maclouf JM Polak (1999) ArticleTitleCytokine-induced prostaglandin E2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide-dependent and -independent mechanism in rat osteoblasts in vitro J Biol Chem 274 1776–1782 Occurrence Handle9880560 Occurrence Handle1:CAS:528:DyaK1MXpsFOmsA%3D%3D Occurrence Handle10.1074/jbc.274.3.1776
K Kagaya K Watanabe Y Fukazawa (1989) ArticleTitleCapacity of recombinant gamma interferon to activate macrophages for Salmonella-killing activity Infect Immun 57 609–615 Occurrence Handle2492266 Occurrence Handle1:CAS:528:DyaL1MXhtlegsb4%3D
F Garcia-del Portillo MB Zwick KY Leung BB Finlay (1993) ArticleTitleSalmonella induces the formation of filamentous structures containing lysosomal membrane glycoproteins in epithelial cells Proc Natl Acad Sci U S A 90 10544–10548 Occurrence Handle8248143 Occurrence Handle1:CAS:528:DyaK2cXltFCrsg%3D%3D Occurrence Handle10.1073/pnas.90.22.10544
S Sato F Nomura T Kawai O Takeuchi PF Muhlradt K Takeda S Akira (2000) ArticleTitleSynergy and cross-tolerance between toll-like receptor (TLR) 2- and TLR4-mediated signaling pathways J Immunol 165 7096–7101 Occurrence Handle11120839 Occurrence Handle1:CAS:528:DC%2BD3cXovFygs7s%3D
K Kobayashi LD Hernandez JE Galán CA Janeway SuffixJr R Medzhitov RA Flavell (2002) ArticleTitleIRAK-M is a negative regulator of Toll-like receptor signaling Cell 110 191–202 Occurrence Handle12150927 Occurrence Handle1:CAS:528:DC%2BD38XlvV2htrw%3D Occurrence Handle10.1016/S0092-8674(02)00827-9
R Nakagawa T Naka H Tsutsui M Fujimoto A Kimura T Abe E Seki S Sato O Takeuchi K Takeda et al. (2002) ArticleTitleSOCS-1 participates in negative regulation of LPS responses Immunity 17 677–687 Occurrence Handle12433373 Occurrence Handle1:CAS:528:DC%2BD38XovF2ls7w%3D Occurrence Handle10.1016/S1074-7613(02)00449-1
I Kinjyo T Hanada K Inagaki-Ohara H Mori D Aki M Ohishi H Yoshida M Kubo A Yoshimura (2002) ArticleTitleSOCS1/JAB is a negative regulator of LPS-induced macrophage activation Immunity 17 583–591 Occurrence Handle12433365 Occurrence Handle1:CAS:528:DC%2BD38XovF2lsro%3D Occurrence Handle10.1016/S1074-7613(02)00446-6
LW Schrum KL Bost MC Hudson I Marriott (2003) ArticleTitleBacterial infection induces expression of functional MHC class II molecules in murine and human osteoblasts Bone (NY) 33 812–821 Occurrence Handle1:CAS:528:DC%2BD3sXovVemt74%3D
KT Stanley C Vandort C Motyl J Endres DA Fox (2006) ArticleTitleImmunocompetent properties of human osteoblasts: interactions with T lymphocytes J Bone Miner Res 21 29–36 Occurrence Handle16355271 Occurrence Handle1:CAS:528:DC%2BD28Xpt1Sntw%3D%3D Occurrence Handle10.1359/JBMR.051004
H Takayanagi S Kim K Matsuo H Suzuki T Suzuki K Sato T Yokichi H Oda K Nakamura N Ida et al. (2002) ArticleTitleRANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β Nature (Lond) 416 744–749 Occurrence Handle1:CAS:528:DC%2BD38XjtVKksLo%3D Occurrence Handle10.1038/416744a
N Kurihara D Bertolini T Suda Y Akiyama GD Roodman (1990) ArticleTitleIL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release J Immunol 144 4226–4230 Occurrence Handle2341718 Occurrence Handle1:CAS:528:DyaK3cXksFOisbY%3D
X Zhang JE Aubin TH Kim U Payne B Chiu RD Inman (2004) ArticleTitleSynovial fibroblasts infected with Salmonella enterica serovar Typhimurium mediate osteoclast differentiation and activation Infect Immun 72 7183–7189 Occurrence Handle15557643 Occurrence Handle1:CAS:528:DC%2BD2cXhtVGls7vO Occurrence Handle10.1128/IAI.72.12.7183-7189.2004
M Takami N Kim J Rho Y Choi (2002) ArticleTitleStimulation by toll-like receptors inhibits osteoclast differentiation J Immunol 169 1516–1523 Occurrence Handle12133979 Occurrence Handle1:CAS:528:DC%2BD38XlslWht7c%3D
V Asensi E Valle A Meana J Fierer A Celada V Alvarez J Paz E Coto JA Carton JA Maradona et al. (2004) ArticleTitleIn vivo interleukin-6 protects neutrophils from apoptosis in osteomyelitis Infect Immun 72 3823–3828 Occurrence Handle15213123 Occurrence Handle1:CAS:528:DC%2BD2cXlslWju70%3D Occurrence Handle10.1128/IAI.72.7.3823-3828.2004
PH Warnke IN Springer PA Russo J Wiltfang H Essig M Kosmahl E Sherry Y Acil (2006) ArticleTitleInnate immunity in human bone Bone (NY) 38 400–408 Occurrence Handle1:CAS:528:DC%2BD28XhslyrtLo%3D
SH Ralston D Todd M Helfrich N Benjamin PS Grabowski (1994) ArticleTitleHuman osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase Endocrinology 135 330–336 Occurrence Handle7516867 Occurrence Handle1:CAS:528:DyaK2cXksl2ntr8%3D Occurrence Handle10.1210/en.135.1.330
K Matsuo DL Galson C Zhao L Peng C Laplace KZ Wang MA Bachler H Amano H Aburatani H Ishikawa et al. (2004) ArticleTitleNuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos J Biol Chem 279 26475–26480 Occurrence Handle15073183 Occurrence Handle1:CAS:528:DC%2BD2cXkvVWgtr4%3D Occurrence Handle10.1074/jbc.M313973200
N Ray M Kuwahara Y Takada K Maruyama T Kawaguchi H Tsubone H Ishikawa K Matsuo (2006) ArticleTitlec-Fos suppresses systemic systemic inflammatory response to endotoxin Int Immunol 18 671–677 Occurrence Handle16569682 Occurrence Handle1:CAS:528:DC%2BD28XktlSis7s%3D Occurrence Handle10.1093/intimm/dxl004
AE Grigoriadis K Schellander ZQ Wang EF Wagner (1993) ArticleTitleOsteoblasts are target cells for transformation in c-fos transgenic mice J Cell Biol 122 685–701 Occurrence Handle8335693 Occurrence Handle1:CAS:528:DyaK3sXltFCmu74%3D Occurrence Handle10.1083/jcb.122.3.685
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Maruyama, K., Sano, Gi. & Matsuo, K. Murine osteoblasts respond to LPS and IFN-γ similarly to macrophages. J Bone Miner Metab 24, 454–460 (2006). https://doi.org/10.1007/s00774-006-0708-x
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DOI: https://doi.org/10.1007/s00774-006-0708-x