Secreted Factors From Intervertebral Disc Cells and Infiltrating Macrophages Promote Degenerated Intervertebral Disc Catabolism.
Journal
Spine
ISSN: 1528-1159
Titre abrégé: Spine (Phila Pa 1976)
Pays: United States
ID NLM: 7610646
Informations de publication
Date de publication:
01 May 2019
01 May 2019
Historique:
pubmed:
13
12
2018
medline:
21
6
2019
entrez:
13
12
2018
Statut:
ppublish
Résumé
Rat nucleus pulposus (NP) cells or annulus fibrosus (AF) cells were stimulated with conditioned media of RAW 264.7 macrophages and vice versa under healthy culture conditions and in the presence of pro-inflammatory mediators. The gene expression of pro-inflammatory mediators, extracellular matrix (ECM)-modifying enzymes, and chemokines, which play important roles in intervertebral disc degeneration (IDD), was determined. To test whether the interaction between native disc cells and infiltrating macrophages accelerates inflammation state, disrupts matrix homeostasis, and promotes inflammatory cells infiltration. With macrophages infiltration, the disc resident cells would be inevitably exposed to macrophages. Macrophages have been shown to play pro-inflammatory role in the cellular interactions with disc cells under healthy culture conditions. However, the biologic interactions between macrophages and disc cells under degenerated disc inflammatory environment remain unknown. Murine Macrophages RAW 264.7 were cultured in the conditioned media of Rat AF or NP cells culture in the presence or absence of IL-1β stimulation. Similarly, Rat AF or NP cells were also cultured in the conditioned media of Murine Macrophages RAW 264.7 culture in the presence or absence of IFN-γ stimulation. The mRNA levels difference of pro-inflammatory genes, catabolic genes and chemokines genes for AF cells, NP cells and Macrophages RAW 264.7 were analyzed by qRT-PCR, respectively. Compared with serum-free media exposure, RAW 264.7 macrophages exposed to AF or NP cells conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of RAW 264.7 macrophages to conditioned media from AF or NP cells with IL-1β stimulation dramatically increased mRNA levels of all the investigated cytokines. Similarly, compared with serum-free media exposure, AF or NP cells exposed to RAW 264.7 macrophages conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of AF or NP cells to conditioned media from RAW 264.7 macrophages with IFN-γ stimulation dramatically increased mRNA levels of all the investigated cytokines. The biologic interactions between infiltrating macrophages and native disc cells under degenerated disc inflammatory environment lead to an increasingly severe inflammatory conditions, which may be a self-stimulated process from the macrophages infiltration occurrenceLevel of Evidence: 5.
Sections du résumé
STUDY DESIGN
METHODS
Rat nucleus pulposus (NP) cells or annulus fibrosus (AF) cells were stimulated with conditioned media of RAW 264.7 macrophages and vice versa under healthy culture conditions and in the presence of pro-inflammatory mediators. The gene expression of pro-inflammatory mediators, extracellular matrix (ECM)-modifying enzymes, and chemokines, which play important roles in intervertebral disc degeneration (IDD), was determined.
OBJECTIVE
OBJECTIVE
To test whether the interaction between native disc cells and infiltrating macrophages accelerates inflammation state, disrupts matrix homeostasis, and promotes inflammatory cells infiltration.
SUMMARY OF BACKGROUND DATA
BACKGROUND
With macrophages infiltration, the disc resident cells would be inevitably exposed to macrophages. Macrophages have been shown to play pro-inflammatory role in the cellular interactions with disc cells under healthy culture conditions. However, the biologic interactions between macrophages and disc cells under degenerated disc inflammatory environment remain unknown.
METHODS
METHODS
Murine Macrophages RAW 264.7 were cultured in the conditioned media of Rat AF or NP cells culture in the presence or absence of IL-1β stimulation. Similarly, Rat AF or NP cells were also cultured in the conditioned media of Murine Macrophages RAW 264.7 culture in the presence or absence of IFN-γ stimulation. The mRNA levels difference of pro-inflammatory genes, catabolic genes and chemokines genes for AF cells, NP cells and Macrophages RAW 264.7 were analyzed by qRT-PCR, respectively.
RESULTS
RESULTS
Compared with serum-free media exposure, RAW 264.7 macrophages exposed to AF or NP cells conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of RAW 264.7 macrophages to conditioned media from AF or NP cells with IL-1β stimulation dramatically increased mRNA levels of all the investigated cytokines. Similarly, compared with serum-free media exposure, AF or NP cells exposed to RAW 264.7 macrophages conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of AF or NP cells to conditioned media from RAW 264.7 macrophages with IFN-γ stimulation dramatically increased mRNA levels of all the investigated cytokines.
CONCLUSION
CONCLUSIONS
The biologic interactions between infiltrating macrophages and native disc cells under degenerated disc inflammatory environment lead to an increasingly severe inflammatory conditions, which may be a self-stimulated process from the macrophages infiltration occurrenceLevel of Evidence: 5.
Identifiants
pubmed: 30540714
doi: 10.1097/BRS.0000000000002953
pii: 00007632-201905010-00005
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
E520-E529Références
Balague F, Mannion AF, Pellise F, et al. Non-specific low back pain. Lancet 2012; 379:482–491.
Katz JN. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am 2006; 88:21–24.
Luoma K, Riihimäki H, Luukkonen R, et al. Low back pain in relation to lumbar disc degeneration. Spine (Phila Pa 1976) 2000; 25:487–492.
Yang H, Liu H, Li Z, et al. Low back pain associated with lumbar disc herniation: role of moderately degenerative disc and annulus fibrous tears. Int J Clin Exp Med 2015; 8:1634–1644.
Le Maitre CL, Hoyland JA, Freemont AJ. Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNF alpha expression profile. Arthritis Res Ther 2007; 9:R77.
Li Z, Liu H, Yang H, et al. Both expression of cytokines and posterior annulus fibrosus rupture are essential for pain behavior changes induced by degenerative intervertebral disc: an experimental study in rats. J Orthop Res 2014; 32:262–272.
Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol 2014; 10:44–56.
Seguin CA, Pilliar RM, Roughley PJ, et al. Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue. Spine (Phila Pa 1976) 2005; 30:1940–1948.
Seguin CA, Bojarski M, Pilliar RM, et al. Differential regulation of matrix degrading enzymes in a TNF alpha induced model of nucleus pulposus tissue degeneration. Matrix Biol 2006; 25:409–418.
Wei Y, Zhi-Hong W, Gui-Xing Q, et al. Extracellular signal-regulated kinase inhibition modulates rat annulus fibrosus cell response to interleukin-1. Spine (Phila Pa 1976) 2013; 38:E1075–E1081.
Yang H, Gao F, Li X, et al. TGF-b1 antagonizes TNF-a induced up-regulation of matrix metalloproteinase 3 in nucleus pulposus cells: role of the ERK1/2 pathway. Connect Tissue Res 2015; 56:461–468.
Shamji MF, Setton LA, Jarvis W, et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum 2010; 62:1974–1982.
Peng B, Hao J, Hou S, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine (Phila Pa 1976) 2006; 31:560–566.
Peng B, Wu W, Hou S, et al. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br 2005; 87:62–67.
Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nature Rev Immunol 2008; 8:958–969.
Lavin Y, Winter D, Blecher-Gonen R, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 2014; 159:1312–1326.
Nakazawa KR, Walter BA, Laudier DM, et al. Accumulation and localization of macrophage phenotypes with human intervertebral disc degeneration. Spine J 2018; 18:343–356.
Zhu L, Zhao Q, Yang T, et al. Cellular metabolism and macrophage functional polarization. Int Rev Immunol 2015; 34:82–100.
Kim JH, Studer RK, Sowa GA, et al. Activated macrophage-like THP-1 cells modulate annulus fibrosus cell production of inflammatory mediators in response to cytokines. Spine (Phila Pa 1976) 2008; 33:2253–2259.
Hamamoto H, Miyamoto H, Doita M, et al. Capability of nondegenerated and degenerated discs in producing inflammatory agents with or without macrophage interaction. Spine (Phila Pa 1976) 2012; 37:161–167.
Yang H, Liu H, Li X, et al. TNF-α and TGF-β1 regulate Syndecan-4 expression in nucleus pulposus cells: role of the mitogen-activated protein kinase and NF-kB pathways. Connect Tissue Res 2015; 56:281–287.
Yu XH, Zhang J, Zheng XL, et al. Interferon-γ in foam cell formation and progression of atherosclerosis. Clin Chim Acta 2015; 441:33–43.
Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther 2005; 7:R732–R745.
Studer RK, Vo N, Sowa G, et al. Human nucleus pulposus cells react to IL-6: independent actions and amplification of response to IL-1 and TNF-α. Spine (Phila Pa 1976) 2011; 36:593–599.
Ferreira SH, Nakamura M, de Abreu Castro MS. The hyperalgesic effects of prostacyclin and prostaglandin E2. Prostaglandins 1978; 16:31–37.
Whelan CJ, Head SA, Poll CT, et al. Prostaglandin (PG) modulation of bradykinin-induced hyperalgesia and oedema in the guinea-pig paw—effects of PGD2, PGE2 and PGI2. Agents Actions Suppl 1991; 32:107–111.
Miyamoto H, Saura R, Doita M, et al. The role of cyclooxygenase-2 in lumbar disc herniation. Spine (Phila Pa 1976) 2002; 27:2477–2483.
Gruber HE, Hoelscher GL, Ingram JA, et al. Proinflammatory cytokines modulate the chemokine CCL2 (MCP-1) in human annulus cells in vitro: CCL2 expression and production. Exp Mol Pathol 2015; 98:102–105.
Wang J, Tian Y, Phillips KL, et al. Tumor necrosis factor α- and interleukin-1β- dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1. Arthritis Rheum 2013; 65:832–842.
Zhang Y, Liu L, Wang S, et al. Production of CCL20 on nucleus pulposus cells recruits IL-17-producing cells to degenerated IVD tissues in rat models. J Mol Histol 2016; 47:81–89.
Vo NV, Hartman RA, Yurube T, et al. Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J 2013; 13:331–341.
Wang WJ, Yu XH, Wang C, et al. MMPs and ADAMTSs in intervertebral disc degeneration. Clin Chim Acta 2015; 448:238–246.
Le Maitre CL, Freemont AJ, Hoyland JA. Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol 2004; 204:47–54.
Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92:827–839.
Millward-Sadler SJ, Costello PW, Freemont AJ, et al. Regulation of catabolic gene expression in normal and degenerate human intervertebral disc cells: implications for the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther 2009; 11:R65.
Goupille P, Jayson MI, Valat JP, et al. Matrix metalloproteinases: the clue to intervertebral disc degeneration? Spine (Phila Pa 1976) 1998; 23:1612–1626.
Liu C, Yang H, Gao F, et al. Resistin promotes intervertebral disc degeneration by upregulation of ADAMTS-5 through p38 MAPK signaling pathway. Spine (Phila Pa 1976) 2016; 41:1414–1420.