Interleukin-1β and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue
Tóm tắt
Formation of terminal complement complex (TCC), a downstream complement system activation product inducing inflammatory processes and cell lysis, has been identified in degenerated discs. However, it remains unclear which molecular factors regulate complement activation during disc degeneration (DD). This study investigated a possible involvement of the pro-inflammatory cytokine interleukin-1β (IL-1β) and the lysosomal protease cathepsin D (CTSD). Disc biopsies were collected from patients suffering from DD (n = 43) and adolescent idiopathic scoliosis (AIS, n = 13). Standardized tissue punches and isolated cells from nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) were stimulated with 5% human serum (HS) alone or in combination with IL-1β, CTSD or zymosan. TCC formation and modulation by the complement regulatory proteins CD46, CD55 and CD59 were analysed. In DD tissue cultures, IL-1β stimulation decreased the percentage of TCC + cells in AF and EP (P < 0.05), whereas CTSD stimulation significantly increased TCC deposition in NP (P < 0.01) and zymosan in EP (P < 0.05). Overall, the expression of CD46, CD55 and CD59 significantly increased in all isolated cells during culture (P < 0.05). Moreover, cellular TCC deposition was HS concentration dependent but unaffected by IL-1β, CTSD or zymosan. These results suggest a functional relevance of IL-1β and CTSD in modulating TCC formation in DD, with differences between tissue regions. Although strong TCC deposition may represent a degeneration-associated event, IL-1β may inhibit it. In contrast, TCC formation was shown to be triggered by CTSD, indicating a multifunctional involvement in disc pathophysiology.
Tài liệu tham khảo
Cheung KMC, Karppinen J, Chan D, Ho DWH, Song YQ, Sham P et al (2009) Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine Phila Pa 1976 34:934–940. https://doi.org/10.1097/BRS.0b013e3181a01b3f
Duance VC, Crean JK, Sims TJ, Avery N, Smith S, Menage J et al (1998) Changes in collagen cross-linking in degenerative disc disease and scoliosis. Spine Phila Pa 1976 23:2545–2551. https://doi.org/10.1097/00007632-199812010-00009
Pokharna HK, Phillips FM (1998) Collagen crosslinks in human lumbar intervertebral disc aging. Spine Phila Pa 1976 23:1645–168. https://doi.org/10.1097/00007632-199808010-00005
Capossela S, Schläfli P, Bertolo A, Janner T, Stadler BM, Pötzel T et al (2014) Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins. Eur Cell Mater 27:251–263. https://doi.org/10.22203/ecm.v027a18
Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine Phila Pa 1976 31:2151–2161. https://doi.org/10.1097/01.brs.0000231761.73859.2c
Vergroesen PP, Kingma I, Emanuel KS, Hoogendoorn RJW, Welting TJ, van Royen BJ et al (2015) Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthr Cartil 23:1057–1070. https://doi.org/10.1016/j.joca.2015.03.028
Ariga K, Yonenobu K, Nakase T, Kaneko M, Okuda S, Uchiyama Y et al (2001) Localization of cathepsins D, K, and L in degenerated human intervertebral discs. Spine Phila Pa 1976 26:2666–2672. https://doi.org/10.1097/00007632-200112150-00007
Molinos M, Almeida CR, Caldeira J, Cunha C, Gonçalves RM, Barbosa MA (2015) Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface 12:20141191. https://doi.org/10.1098/rsif.2014.1191
Risbud MV, Shapiro IM (2014) Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol 10:44–56. https://doi.org/10.1038/nrrheum.2013.160
Teixeira GQ, Gonçalves RM, Barobosa MA (2018) Immunomodulation in degenerated intervertebral disc. In: Gonçalves RM, Barbosa MA (eds) Gene and cell delivery for intervertebral disc degeneration, 1st edn. CRC Press, Boca Raton, p 48
Ricklin D, Lambris JD (2013) Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol 190:3831–3838. https://doi.org/10.4049/jimmunol.1203487
Morgan BP (2016) The membrane attack complex as an inflammatory trigger. Immunobiology 221:747–751. https://doi.org/10.1016/j.imbio.2015.04.006
Grönblad M, Habtemariam A, Virri J, Seitsalo S, Vanharanta H, Guyer RD (2003) Complement membrane attack complexes in pathologic disc tissues. Spine Phila Pa 1976 28:114–118. https://doi.org/10.1097/00007632-200301150-00004
Teixeira GQ, Yong Z, Goncalves RM, Kuhn A, Riegger J, Brisby H et al (2020) Terminal complement complex formation is associated with intervertebral disc degeneration. Eur Spine J 30:217–226. https://doi.org/10.1007/s00586-020-06592-4
Ruiz-Argüelles A, Llorente L (2007) The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias. Autoimmun Rev 6:155–161. https://doi.org/10.1016/j.autrev.2006.09.008
Johnson E, Berge V, Høgåsen K (1994) Formation of the terminal complement complex on agarose beads: further evidence that vitronectin (complement S-protein) inhibits C9 polymerization. Scand J Immunol 39:281–285. https://doi.org/10.1111/j.1365-3083.1994.tb03372.x
Jeon H, Lee JS, Yoo S, Lee MS (2014) Quantification of complement system activation by measuring C5b–9 cell surface deposition using a cell-ELISA technique. J Immunol Methods 415:57–62. https://doi.org/10.1016/j.jim.2014.09.002
Johnson ZI, Schoepflin ZR, Choi H, Shapiro IM, Risbud MV (2015) Disc in flames: roles of TNF-α and IL-1β in intervertebral disc degeneration. Eur Cells Mater 30:104–117. https://doi.org/10.22203/ecm.v030a08
Morimoto R, Akeda K, Iida R, Nishimura A, Tsujii M, Obata S et al (2013) Tissue renin-angiotensin system in the intervertebral disc. Spine Phila Pa 1976 38:E129–E136. https://doi.org/10.1097/BRS.0b013e31827b8c89
Li Z, Wystrach L, Bernstein A, Grad S, Alini M, Richards RG et al (2020) The tissue-renin-angiotensin-system of the human intervertebral disc. Eur Cell Mater 40:115–132. https://doi.org/10.22203/eCM.v040a07
Smith MC, Pensky J, Naff GB (1982) Inhibition of zymosan-induced alternative complement pathway activation by concanavalin A. Infect Immun 38:1279–1284. https://doi.org/10.1128/IAI.38.3.1279-1284.1982
Rahat MA, Brod V, Amit-Cohen BC, Henig O, Younis S, Bitterman H (2016) Oxygen mitigates the inflammatory response in a model of hemorrhage and zymosan-induced inflammation. Shock 45:198–208. https://doi.org/10.1097/SHK.0000000000000492
Mazur-Bialy AI, Pocheć E (2016) HMGB1 inhibition during zymosan-induced inflammation: the potential therapeutic action of riboflavin. Arch Immunol Ther Exp Warsz 64:171–176. https://doi.org/10.1007/s00005-015-0366-6
Lima JBM, Veloso CC, Vilela FC, Giusti-Paiva A (2017) Prostaglandins mediate zymosan-induced sickness behavior in mice. J Physiol Sci 67:673–679. https://doi.org/10.1007/s12576-016-0494-8
Ivanov PA, Faktor MI, Karpova NS, Cheremnykh EG, Brusov OS (2016) Complement-mediated death of ciliate tetrahymena pyriformis caused by human blood serum. Bull Exp Biol Med 160:775–778. https://doi.org/10.1007/s10517-016-3307-4
Yoshida M, Nakamura T, Sei A, Kikuchi T, Takagi K, Matsukawa A (2005) Intervertebral disc cells produce tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model. Spine Phila Pa 1976 30:55–61. https://doi.org/10.1097/01.brs.0000149194.17891.bf
Zhang Q, Wang H, Mao C, Sun M, Dominah G, Chen L et al (2018) Fatty acid oxidation contributes to IL-1β secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol 94:27–35. https://doi.org/10.1016/j.molimm.2017.12.011
Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573. https://doi.org/10.1016/j.cardiores.2005.12.002
Lin LR, Liu W, Zhu XZ, Chen YY, Gao ZX, Gao K et al (2018) Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1β production. BMC Immunol 19:28. https://doi.org/10.1186/s12865-018-0265-9
Moon MR, Parikh AA, Pritts TA, Kane C, Fischer JE, Salzman AL et al (2000) Interleukin-1beta induces complement component C3 and IL-6 production at the basolateral and apical membranes in a human intestinal epithelial cell line. Shock 13:374–378. https://doi.org/10.1097/00024382-200005000-00005
Yang S, Li L, Zhu L, Zhang C, Li Z, Guo Y et al (2019) Aucubin inhibits IL-1bβ- or TNF-α-induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR-140-5p/CREB1 axis. J Cell Physiol 234:13639–13648. https://doi.org/10.1002/jcp.28044
Batra R, Suh MK, Carson JS, Dale MA, Meisinger TM, Fitzgerald M et al (2018) IL-1β (interleukin-1β) and TNF-α (tumor necrosis factor-α) impact abdominal aortic aneurysm formation by differential effects on macrophage polarization. Arterioscler Thromb Vasc Biol 38:457–463. https://doi.org/10.1161/ATVBAHA.117.310333
Busch C, Girke G, Kohl B, Stoll C, Lemke M, Krasnici S et al (2013) Complement gene expression is regulated by pro-inflammatory cytokines and the anaphylatoxin C3a in human tenocytes. Mol Immunol 53:363–373. https://doi.org/10.1016/j.molimm.2012.09.001
Asgari E, Le Friec G, Yamamoto H, Perucha E, Sacks SS, Köhl J et al (2013) C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation. Blood 122:3473–3481. https://doi.org/10.1182/blood-2013-05-502229
Schindler R, Gelfand JA, Dinarello CA (1990) Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. Blood 76:1631–1638. https://doi.org/10.1182/blood.V76.8.1631.1631
Hyc A, Osiecka-Iwan A, Strzelczyk P, Moskalewski S (2003) Effect of IL-1beta, TNF-alpha and IL-4 on complement regulatory protein mRNA expression in human articular chondrocytes. Int J Mol Med 11:91–94. https://doi.org/10.3892/ijmm.11.1.91
Terai I, Kobayashi K, Matsushita M, Fujita T, Matsuno K (1995) α2-Macroglobulin binds to and inhibits mannose-binding protein-associated serine protease. Int Immunol 7:1579–1584. https://doi.org/10.1093/intimm/7.10.1579
Borth W, Urbanski A, Prohaska R, Susanj M, Luger TA (1990) Binding of recombinant interleukin-1β to the third complement component and α2-macroglobulin after activation of serum by immune complexes. Blood 75:2388–2395. https://doi.org/10.1182/blood.V75.12.2388.2388
Huber-Lang M, Denk S, Fulda S, Erler E, Kalbitz M, Weckbach S et al (2012) Cathepsin D is released after severe tissue trauma in vivo and is capable of generating C5a in vitro. Mol Immunol 50:60–65. https://doi.org/10.1016/j.molimm.2011.12.005
Handley CJ, Mok MT, Ilic MZ, Adcocks C, Buttle DJ, Robinson HC (2001) Cathepsin D cleaves aggrecan at unique sites within the interglobular domain and chondroitin sulfate attachment regions that are also cleaved when cartilage is maintained at acid pH. Matrix Biol 20:543–553. https://doi.org/10.1016/s0945-053x(01)00168-8
Riegger J, Huber-Lang M, Brenner RE (2020) Crucial role of the terminal complement complex in chondrocyte death and hypertrophy after cartilage trauma. Osteoarthr Cartil 28:685–697. https://doi.org/10.1016/j.joca.2020.01.004
Wang Q, Rozelle AL, Lepus CM, Scanzello CR, Song JJ, Larsen DM et al (2011) Identification of a central role for complement in osteoarthritis. Nat Med 17:1674–1679. https://doi.org/10.1038/nm.2543