Top

Published in:

01-06-2020 | Original Article

Nicotinamide Phosphoribosyl Transferase Controls NLRP3 Inflammasome Activity Through MAPK and NF-κB Signaling in Nucleus Pulposus Cells, as Suppressed by Melatonin

Authors: Yingjie Huang, Yan Peng, Jianchao Sun, Shuangxing Li, Junmin Hong, Jie Zhou, Jianchong Chen, Jiansen Yan, Zhengqi Huang, Xiaofei Wang, Weijian Chen, Wei Ye

Published in: Inflammation | Issue 3/2020

Abstract

Intervertebral disc degeneration (IDD) is characterized by an imbalance between matrix synthesis and degradation in intervertebral discs. However, the causes of this imbalance remain elusive. Previous studies revealed that NLRP3 inflammasome plays a vital role in IDD and nicotinamide phosphoribosyl transferase (NAMPT) is involved in matrix degradation induced by IL-1β. In the current study, real-time PCR, western blot and NAMPT knockdown, or overexpression experiments were used to detect the regulatory effects of NAMPT on NLRP3 inflammasome activity in nucleus pulposus (NP) cells. The results revealed that NAMPT downregulation or overexpression controlled the matrix degradation induced by TNF-α by modulating NLRP3 inflammasome activity. Moreover, the NAMPT inhibition study demonstrated MAPK and NF-κB signaling play a key role in above process. In addition, melatonin was reported to play a protective role in matrix metabolism of NP cells. Herein, real-time PCR, western blot analysis, and immunofluorescence staining experiments revealed that melatonin showed protective effects against TNF-α-induced matrix degradation by downregulating NAMPT and reducing NLRP3 inflammasome activity in NP cells. The current investigation verified that melatonin could alleviate matrix degradation induced by TNF-α by suppressing NAMPT and NLRP3 inflammasome activity. Moreover, NAMPT downregulation controlled the matrix degradation induced by TNF-α by suppressing NLRP3 inflammasome activity through MAPK and NF-κB signaling in NP cells.

Roughley, P.J. 2004. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine 29 (23): 2691–2699. https://doi.org/10.1097/01.brs.0000146101.53784.b1.

Dagenais, S., J. Caro, and S. Haldeman. 2008. A systematic review of low back pain cost of illness studies in the United States and internationally. The Spine Journal 8 (1): 8–20. https://doi.org/. https://doi.org/10.1016/j.spinee.2007.10.005.

Maher C., M. Underwood, R. Buchbinder. 2017. Non-specific low back pain. Lancet. 389 (10070): 736–747. https://doi.org/10.1016/S0140-6736(16)30970-9.

DePalma, M.J., J.M. Ketchum, and T. Saullo. 2011. What is the source of chronic low back pain and does age play a role? Pain Medicine 12 (2): 224–233. https://doi.org/10.1111/j.1526-4637.2010.01045.x.

Kepler, C.K., R.K. Ponnappan, C.A. Tannoury, M.V. Risbud, and D.G. Anderson. 2013. The molecular basis of intervertebral disc degeneration. The Spine Journal 13 (3): 318–330. https://doi.org/10.1016/j.spinee.2012.12.003.

Colombier, P., J. Clouet, O. Hamel, L. Lescaudron, and J. Guicheux. 2014. The lumbar intervertebral disc: from embryonic development to degeneration. Joint, Bone, Spine 81 (2): 125–129. https://doi.org/10.1016/j.jbspin.2013.07.012.

Adams, M.A., P. Dolan, and D.S. McNally. 2009. The internal mechanical functioning of intervertebral discs and articular cartilage, and its relevance to matrix biology. Matrix Biology 28 (7): 384–389. https://doi.org/10.1016/j.matbio.2009.06.004.

Zhou, J., J. Sun, D.Z. Markova, S. Li, C.K. Kepler, J. Hong, Y. Huang, W. Chen, K. Xu, F. Wei, and W. Ye. 2019. MicroRNA-145 overexpression attenuates apoptosis and increases matrix synthesis in nucleus pulposus cells. Life Sciences 221: 274–283. https://doi.org/10.1016/j.lfs.2019.02.041.

Risbud, M.V., and I.M. Shapiro. 2014. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nature Reviews Rheumatology 10 (1): 44–56. https://doi.org/10.1038/nrrheum.2013.160.

10.

Jin, H., Q. Wang, J. Wu, J. Han, T. Qian, Z. Zhang, J. Wang, X. Pan, A. Wu, and X. Wang. 2019. Baicalein inhibits the IL-1β-induced inflammatory response in nucleus pulposus cells and attenuates disc degeneration in vivo. Inflammation 42 (3): 1032–1044. https://doi.org/10.1007/s10753-019-00965-8.

11.

Wu, X., S. Li, K. Wang, W. Hua, S. Li, Y. Song, Y. Zhang, S. Yang, and C. Yang. 2019. TNF-α regulates ITGβ1 and SYND4 expression in nucleus pulposus cells: activation of FAK/PI3K signaling. Inflammation 42: 1575–1584. https://doi.org/10.1007/s10753-019-01019-9.

12.

Song, Y., Y. Wang, Y. Zhang, W. Geng, W. Liu, Y. Gao, S. Li, K. Wang, X. Wu, L. Kang, and C. Yang. 2017. Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells. Journal of Cellular and Molecular Medicine 21 (7): 1373–1387. https://doi.org/10.1111/jcmm.13067.

13.

Dong, H.C., P.N. Li, C.J. Chen, X. Xu, H. Zhang, G. Liu, L.J. Zheng, and P. Li. 2019. Sinomenine attenuates cartilage degeneration by regulating miR-223-3p/NLRP3 inflammasome signaling. Inflammation 42 (4): 1265–1275. https://doi.org/10.1007/s10753-019-00986-3.

14.

Shi, J., W. Gao, and F. Shao. 2017. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem. Sci. 42 (4): 245–254. https://doi.org/10.1016/j.tibs.2016.10.004.

15.

Kovacs, S.B., and E.A. Miao. 2017. Gasdermins: effectors of pyroptosis. Trends in Cell Biology 27 (9): 673–684. https://doi.org/10.1016/j.tcb.2017.05.005 .

16.

Dahl, T.B., S. Holm, P. Aukrust, and B. Halvorsen. 2012. Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and pathophysiology. Annual Review of Nutrition 32: 229–243. https://doi.org/10.1146/annurev-nutr-071811-150746.

17.

Shi, C., H. Wu, D. Du, H.J. Im, Y. Zhang, B. Hu, H. Chen, X. Wang, Y. Liu, P. Cao, Y. Tian, X. Shen, R. Gao, A.J. van Wijnen, X. Ye, and W. Yuan. 2018. Nicotinamide phosphoribosyltransferase inhibitor APO866 prevents IL-1β-induced human nucleus pulposus cell degeneration via autophagy. Cellular Physiology and Biochemistry 49 (6): 2463–2482. https://doi.org/10.1159/000493843.

18.

Poeggeler, B. 2005. Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy. Endocrine. 27 (2): 201–212. https://doi.org/10.1385/ENDO:27:2:201.

19.

Jou, M.J., T.I. Peng, P.Z. Yu, S.B. Jou, R.J. Reiter, J.Y. Chen, H.Y. Wu, C.C. Chen, and L.F. Hsu. 2007. Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis. Journal of Pineal Research 43 (4): 389–403. https://doi.org/. https://doi.org/10.1111/j.1600-079X.2007.00490.x.

20.

Nabavi, S.M., S.F. Nabavi, A. Sureda, J. Xiao, A.R. Dehpour, S. Shirooie, A.S. Silva, A. Baldi, H. Khan, and M. Daglia. 2018. Anti-inflammatory effects of melatonin: a mechanistic review. Critical Reviews in Food Science and Nutrition 59: 1–13. https://doi.org/10.1080/10408398.2018.1487927.

21.

Hu, X., D. Li, J. Wang, J. Guo, Y. Li, Y. Cao, N. Zhang, and Y. Fu. 2018. Melatonin inhibits endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in lipopolysaccharide-induced endometritis in mice. International Immunopharmacology 64: 101–109. https://doi.org/10.1016/j.intimp.2018.08.028.

22.

Peng, Z., W. Zhang, J. Qiao, and B. He. 2018. Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD. International Immunopharmacology 62: 23–28. https://doi.org/10.1016/j.intimp.2018.06.033.

23.

Sun, J., J. Hong, S. Sun, X. Wang, Y. Peng, J. Zhou, Y. Huang, S. Li, W. Chen, C. Li, K. Xu, and W. Ye. 2018. Transcription factor 7-like 2 controls matrix degradation through nuclear factor kappaB signaling and is repressed by microRNA-155 in nucleus pulposus cells. Biomedicine & Pharmacotherapy 108: 646–655. https://doi.org/10.1016/j.biopha.2018.09.076.

24.

Wang, X., C. Li, A. Liang, Y. Peng, J. Sun, D. Huang, K. Xu, and W. Ye. 2016. Regulation of a disintegrins and metalloproteinase with thrombospondin motifs 7 during inflammation in nucleus pulposus (NP) cells: role of AP-1, Sp1 and NF-κB signaling. Inflammation Research 65 (12): 951–962. https://doi.org/10.1007/s00011-016-0978-2.

25.

Tian, Y., W. Yuan, N. Fujita, J. Wang, H. Wang, I.M. Shapiro, and M.V. Risbud. 2013. Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1 (ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-κB. The American Journal of Pathology 182 (6): 2310–2321. https://doi.org/10.1016/j.ajpath.2013.02.037.

26.

Xu, K., W. Chen, X. Wang, Y. Peng, A. Liang, D. Huang, C. Li, and W. Ye. 2015. Autophagy attenuates the catabolic effect during inflammatory conditions in nucleus pulposus cells, as sustained by NF-κB and JNK inhibition. International Journal of Molecular Medicine 36 (3): 661–668. https://doi.org/10.3892/ijmm.2015.2280.

27.

Li Z., X. Li, C. Chen, M.T.V. Chan, W.K.K. Wu, J. Shen. 2017. Melatonin inhibits nucleus pulposus (NP) cell proliferation and extracellular matrix (ECM) remodeling via the melatonin membrane receptors mediated PI3K-Akt pathway. J. Pineal Res. 63(3). https://doi.org/10.1111/jpi.12435.

28.

Wang, J., D. Markova, D.G. Anderson, Z. Zheng, I.M. Shapiro, and M.V. Risbud. 2011. TNF-α and IL-1β promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc. The Journal of Biological Chemistry 286 (46): 39738–39749. https://doi.org/10.1074/jbc.M111.264549.

29.

He, R., M. Cui, H. Lin, L. Zhao, J. Wang, S. Chen, and Z. Shao. 2018. Melatonin resists oxidative stress-induced apoptosis in nucleus pulposus cells. Life Sciences 199: 122–130. https://doi.org/10.1016/j.lfs.2018.03.020.

30.

Ma, S., J. Chen, J. Feng, R. Zhang, M. Fan, D. Han, X. Li, C. Li, J. Ren, Y. Wang, and F. Cao. 2018. Melatonin ameliorates the progression of atherosclerosis via mitophagy activation and NLRP3 inflammasome inhibition. Oxidative Medicine and Cellular Longevity 2018: 1–12. https://doi.org/10.1155/2018/9286458.

31.

Ye, W., J. Zhou, D.Z. Markova, Y. Tian, J. Li, D.G. Anderson, I.M. Shapiro, and M.V. Risbud. 2015. Xylosyltransferase-1 expression is refractory to inhibition by the inflammatory cytokines tumor necrosis factor α and IL-1β in nucleus pulposus cells: novel regulation by AP-1, Sp1, and Sp3. The American Journal of Pathology 185 (2): 485–495. https://doi.org/10.1016/j.ajpath.2014.09.021.

32.

Gosset, M., F. Berenbaum, C. Salvat, A. Sautet, A. Pigenet, K. Tahiri, and C. Jacques. 2008. Crucial role of visfatin/pre–B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis and Rheumatism 58 (5): 1399–1409. https://doi.org/10.1002/art.23431.

33.

Brentano, F., O. Schorr, C. Ospelt, J. Stanczyk, R.E. Gay, S. Gay, and D. Kyburz. 2007. Pre–B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis and Rheumatism 56 (9): 2829–2839. https://doi.org/10.1002/art.22833.

34.

Chen, Z.H., S.H. Jin, M.Y. Wang, X.L. Jin, C. Lv, Y.F. Deng, and J.L. Wang. 2015. Enhanced NLRP3, Caspase-1, and IL-1β levels in degenerate human intervertebral disc and their association with the grades of disc degeneration. Anat Rec (Hoboken) 298 (4): 720–726. https://doi.org/10.1002/ar.23059.

35.

Tang, P., R. Zhu, W.P. Ji, J.Y. Wang, S. Chen, S.W. Fan, and Z.J. Hu. 2016. The NLRP3/Caspase-1/interleukin-1beta axis is active in human lumbar cartilaginous endplate degeneration. Clinical Orthopaedics and Related Research 474 (8): 1818–1826. https://doi.org/10.1007/s11999-016-4866-4.

36.

Xia, C., Z. Zeng, B. Fang, M. Tao, C. Gu, L. Zheng, Y. Wang, Y. Shi, C. Fang, S. Mei, Q. Chen, and J. Zhao. 2019. Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects. Free Radical Biology & Medicine 143: 1–15. https://doi.org/10.1016/j.freeradbiomed.2019.07.026.

37.

Bergsbaken, T., S.L. Fink, and B.T. Cookson. 2009. Pyroptosis: host cell death and inflammation. Nature Reviews. Microbiology 7 (2): 99–109. https://doi.org/10.1038/nrmicro2070.

38.

Shi J., W. Gao, F. Shao. 2017. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem. Sci. 42 (): 245–254. https://doi.org/10.1016/j.tibs.2016.10.004.

39.

Liu, L.B., H.F. Shen, W. Cha, Z.J. Jin, H.J. Xia, J.J. Liu, and J.F. Hu. 2019. SXBX pill suppresses homocysteine-induced vascular smooth muscle cells dedifferentiation by inhibiting NLRP3 inflammasomes activation via ERK/p38 MAPK pathways. American Journal of Translational Research 11 (2): 806–818 https://doi.org/.

40.

Su, W.J., Y. Zhang, Y. Chen, H. Gong, Y.J. Lian, W. Peng, Y.Z. Liu, Y.X. Wang, Z.L. You, S.J. Feng, Y. Zong, G.C. Lu, and C.L. Jiang. 2017. NLRP3 gene knockout blocks NF-κB and MAPK signaling pathway in CUMS-induced depression mouse model. Behavioural Brain Research 322: 1–8. https://doi.org/10.1016/j.bbr.2017.01.018.

41.

Zou, J., Y. Yang, Y. Yang, and X. Liu. 2018. Polydatin suppresses proliferation and metastasis of non-small cell lung cancer cells by inhibiting NLRP3 inflammasome activation via NF-κB pathway. Biomedicine & Pharmacotherapy 108: 130–136. https://doi.org/10.1016/j.biopha.2018.09.051.

42.

Guo J.Y., F. Li, Y.B. Wen, H.X. Cui, M.L. Guo, L. Zhang, Y.F. Zhang, Y,J. Guo, Y.X. Guo. 2017. Melatonin inhibits Sirt1-dependent NAMPT and NFAT5 signaling in chondrocytes to attenuate osteoarthritis. Oncotarget 8 (34): 55967–55983. https://doi.org/10.18632/oncotarget.18356.

43.

Hardeland, R. 2018. Melatonin and inflammation-Story of a double-edged blade. J. Pineal Res: 65(4). https://doi.org/10.1111/jpi.12525.

44.

Turgut M., H.K. Başaloğlu, C. Yenisey, 2006. Y. Ozsunar. Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken. Eur. The Spine Journal 15 (5): 605–612. https://doi.org/10.1007/s00586-005-0972-9.

45.

Tang, P., J.M. Gu, Z.A. Xie, Y. Gu, Z.W. Jie, K.M. Huang, J.Y. Wang, S.W. Fan, X.S. Jiang, and Z.J. Hu. 2018. Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway. Free Radical Biology & Medicine 120: 368–379. https://doi.org/. https://doi.org/10.1016/j.freeradbiomed.2018.04.008.

Title: Nicotinamide Phosphoribosyl Transferase Controls NLRP3 Inflammasome Activity Through MAPK and NF-κB Signaling in Nucleus Pulposus Cells, as Suppressed by Melatonin
Authors: Yingjie Huang
Yan Peng
Jianchao Sun
Shuangxing Li
Junmin Hong
Jie Zhou
Jianchong Chen
Jiansen Yan
Zhengqi Huang
Xiaofei Wang
Weijian Chen
Wei Ye
Publication date: 01-06-2020
Publisher: Springer US
Published in: Inflammation / Issue 3/2020
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-019-01166-z

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Nicotinamide Phosphoribosyl Transferase Controls NLRP3 Inflammasome Activity Through MAPK and NF-κB Signaling in Nucleus Pulposus Cells, as Suppressed by Melatonin

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2020

Peiminine Attenuates Acute Lung Injury Induced by LPS Through Inhibiting Lipid Rafts Formation

Study on the Role of Salivary Flora and NF-κB Inflammatory Signal Pathway in Oral Lichen Planus

Cyanidin-3-O-Glucoside Attenuates Lipopolysaccharide-Induced Inflammation in Human Corneal Epithelial Cells by Inducing Let-7b-5p-Mediated HMGA2/PI3K/Akt Pathway

Ellagic Acid Ameliorates Lung Inflammation and Heart Oxidative Stress in Elastase-Induced Emphysema Model in Rat

Correction to: Ghrelin Fights against Titanium Particle-Induced Inflammatory Osteolysis through Activation of β-Catenin Signaling Pathway

ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page