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Published in: Inflammation 1/2016

01-02-2016

Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways

Authors: Zhongbing Liu, Chi Sun, Ran Tao, Xinbao Xu, Libin Xu, Hongbing Cheng, Youhua Wang, Dongmei Zhang

Published in: Inflammation | Issue 1/2016

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Abstract

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient and antioxidant and has been reported to exert potent immunosuppressive effects. However, the therapeutically potential of PQQ on rheumatoid arthritis (RA) has not been explored. In the present study, the anti-inflammatory effects of PQQ were investigated in interleukin (IL)-1β-treated SW982 cells, a RA-like fibroblast-like synoviocytes (FLSs) injury model. Our observations showed that pretreatment with PQQ significantly inhibited the expression of matrix metalloproteinase (MMP)-1 and MMP-3 and suppressed the production of proinflammatory mediators such as TNF-α and IL-6 in IL-1β-treated SW982 cells. The nuclear translocation of nuclear factor kappa B (NF-κB) and the phosphorylation level of p65, p38, and JNK MAP kinase pathways were also inhibited by PQQ in IL-1β-stimulated SW982 cells. To further confirm the therapeutic effects of PQQ on RA in vivo, a collagen-induced arthritis (CIA) model was used. Mice treated with PQQ demonstrated marked attenuation of arthritic symptoms based on histopathology and clinical arthritis scores. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of RA.
Literature
1.
go back to reference Henderson, B., T. Hardingham, S. Blake, and J. Lewthwaite. 1993. Experimental arthritis models in the study of the mechanisms of articular cartilage loss in rheumatoid arthritis. Agents and Actions. Supplements 39: 15–26.PubMed Henderson, B., T. Hardingham, S. Blake, and J. Lewthwaite. 1993. Experimental arthritis models in the study of the mechanisms of articular cartilage loss in rheumatoid arthritis. Agents and Actions. Supplements 39: 15–26.PubMed
2.
go back to reference Han, M.K., J.S. Kim, B.H. Park, J.R. Kim, B.Y. Hwang, H.Y. Lee, E.K. Song, and W.H. Yoo. 2003. NF-kappaB-dependent lymphocyte hyperadhesiveness to synovial fibroblasts by hypoxia and reoxygenation: Potential role in rheumatoid arthritis. Journal of Leukocyte Biology 73: 525–529.CrossRefPubMed Han, M.K., J.S. Kim, B.H. Park, J.R. Kim, B.Y. Hwang, H.Y. Lee, E.K. Song, and W.H. Yoo. 2003. NF-kappaB-dependent lymphocyte hyperadhesiveness to synovial fibroblasts by hypoxia and reoxygenation: Potential role in rheumatoid arthritis. Journal of Leukocyte Biology 73: 525–529.CrossRefPubMed
3.
go back to reference Firestein, G.S. 1996. Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors? Arthritis and Rheumatism 39: 1781–1790.CrossRefPubMed Firestein, G.S. 1996. Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors? Arthritis and Rheumatism 39: 1781–1790.CrossRefPubMed
4.
go back to reference Feldmann, M., and S.R. Maini. 2008. Role of cytokines in rheumatoid arthritis: An education in pathophysiology and therapeutics. Immunology Reviews 223: 7–19.CrossRef Feldmann, M., and S.R. Maini. 2008. Role of cytokines in rheumatoid arthritis: An education in pathophysiology and therapeutics. Immunology Reviews 223: 7–19.CrossRef
5.
go back to reference Bartok, B., and G.S. Firestein. 2010. Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunology Reviews 233: 233–255.CrossRef Bartok, B., and G.S. Firestein. 2010. Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunology Reviews 233: 233–255.CrossRef
6.
go back to reference Baier, A., I. Meineckel, S. Gay, and T. Pap. 2003. Apoptosis in rheumatoid arthritis. Current Opinion in Rheumatology 15: 274–279.CrossRefPubMed Baier, A., I. Meineckel, S. Gay, and T. Pap. 2003. Apoptosis in rheumatoid arthritis. Current Opinion in Rheumatology 15: 274–279.CrossRefPubMed
7.
go back to reference Hah, Y.S., Y.R. Lee, J.S. Jun, H.S. Lim, H.O. Kim, Y.G. Jeong, G.M. Hur, S.Y. Lee, M.J. Chung, J.W. Park, S.I. Lee, and B.H. Park. 2010. A20 suppresses inflammatory responses and bone destruction in human fibroblast-like synoviocytes and in mice with collagen-induced arthritis. Arthritis and Rheumatism 62: 2313–2321.CrossRefPubMed Hah, Y.S., Y.R. Lee, J.S. Jun, H.S. Lim, H.O. Kim, Y.G. Jeong, G.M. Hur, S.Y. Lee, M.J. Chung, J.W. Park, S.I. Lee, and B.H. Park. 2010. A20 suppresses inflammatory responses and bone destruction in human fibroblast-like synoviocytes and in mice with collagen-induced arthritis. Arthritis and Rheumatism 62: 2313–2321.CrossRefPubMed
9.
go back to reference Vallabhapurapu, S., and M. Karin. 2009. Regulation and function of NF-kappaB transcription factors in the immune system. Annual Review of Immunology 27: 693–733.CrossRefPubMed Vallabhapurapu, S., and M. Karin. 2009. Regulation and function of NF-kappaB transcription factors in the immune system. Annual Review of Immunology 27: 693–733.CrossRefPubMed
10.
11.
go back to reference Scheinman, R. 2013. NF-kappaB and rheumatoid arthritis: Will understanding genetic risk lead to a therapeutic reward? Forum on immunopathological diseases and therapeutics 4: 93–110.PubMedCentralCrossRefPubMed Scheinman, R. 2013. NF-kappaB and rheumatoid arthritis: Will understanding genetic risk lead to a therapeutic reward? Forum on immunopathological diseases and therapeutics 4: 93–110.PubMedCentralCrossRefPubMed
12.
go back to reference Schmidt, M., and R.H. Straub. 2015. 11beta-hydroxysteroid dehydrogenase enzymes modulate effects of glucocorticoids in rheumatoid arthritis synovial cells. Neuroimmunomodulation 22: 40–45.CrossRefPubMed Schmidt, M., and R.H. Straub. 2015. 11beta-hydroxysteroid dehydrogenase enzymes modulate effects of glucocorticoids in rheumatoid arthritis synovial cells. Neuroimmunomodulation 22: 40–45.CrossRefPubMed
13.
go back to reference Choi, E.M., and Y.S. Lee. 2010. Luteolin suppresses IL-1beta-induced cytokines and MMPs production via p38 MAPK, JNK, NF-kappaB and AP-1 activation in human synovial sarcoma cell line, SW982. Food and Chemical Toxicology 48: 2607–2611.CrossRefPubMed Choi, E.M., and Y.S. Lee. 2010. Luteolin suppresses IL-1beta-induced cytokines and MMPs production via p38 MAPK, JNK, NF-kappaB and AP-1 activation in human synovial sarcoma cell line, SW982. Food and Chemical Toxicology 48: 2607–2611.CrossRefPubMed
14.
go back to reference Yamazaki, T., T. Yokoyama, H. Akatsu, T. Tukiyama, and T. Tokiwa. 2003. Phenotypic characterization of a human synovial sarcoma cell line, SW982, and its response to dexamethasone. In Vitro Cellular & Developmental Biology: Animal 39: 337–339.CrossRef Yamazaki, T., T. Yokoyama, H. Akatsu, T. Tukiyama, and T. Tokiwa. 2003. Phenotypic characterization of a human synovial sarcoma cell line, SW982, and its response to dexamethasone. In Vitro Cellular & Developmental Biology: Animal 39: 337–339.CrossRef
15.
go back to reference Zhang, Y., P.J. Feustel, and H.K. Kimelberg. 2006. Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat. Brain Research 1094: 200–206.CrossRefPubMed Zhang, Y., P.J. Feustel, and H.K. Kimelberg. 2006. Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat. Brain Research 1094: 200–206.CrossRefPubMed
16.
go back to reference Salisbury, S.A., H.S. Forrest, W.B. Cruse, and O. Kennard. 1979. A novel coenzyme from bacterial primary alcohol dehydrogenases. Nature 280: 843–844.CrossRefPubMed Salisbury, S.A., H.S. Forrest, W.B. Cruse, and O. Kennard. 1979. A novel coenzyme from bacterial primary alcohol dehydrogenases. Nature 280: 843–844.CrossRefPubMed
17.
go back to reference Kong, L., C. Yang, L. Yu, W. Smith, S. Zhu, J. Zhu, and Q. Zhu. 2013. Pyrroloquinoline quinine inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos in mouse bone marrow cells and inhibits wear particle-induced osteolysis in mice. PLoS ONE 8, e61013.PubMedCentralCrossRefPubMed Kong, L., C. Yang, L. Yu, W. Smith, S. Zhu, J. Zhu, and Q. Zhu. 2013. Pyrroloquinoline quinine inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos in mouse bone marrow cells and inhibits wear particle-induced osteolysis in mice. PLoS ONE 8, e61013.PubMedCentralCrossRefPubMed
18.
go back to reference Gallop, P.M., E. Henson, M.A. Paz, S.L. Greenspan, and R. Fluckiger. 1989. Acid-promoted tautomeric lactonization and oxidation-reduction of pyrroloquinoline quinone (PQQ). Biochemical and Biophysical Research Communications 163: 755–763.CrossRefPubMed Gallop, P.M., E. Henson, M.A. Paz, S.L. Greenspan, and R. Fluckiger. 1989. Acid-promoted tautomeric lactonization and oxidation-reduction of pyrroloquinoline quinone (PQQ). Biochemical and Biophysical Research Communications 163: 755–763.CrossRefPubMed
19.
go back to reference Gallop, P.M., M.A. Paz, R. Fluckiger, and E. Henson. 1993. Is the antioxidant, anti-inflammatory putative new vitamin, PQQ, involved with nitric oxide in bone metabolism? Connective Tissue Research 29: 153–161.CrossRefPubMed Gallop, P.M., M.A. Paz, R. Fluckiger, and E. Henson. 1993. Is the antioxidant, anti-inflammatory putative new vitamin, PQQ, involved with nitric oxide in bone metabolism? Connective Tissue Research 29: 153–161.CrossRefPubMed
20.
go back to reference Rucker, R., W. Chowanadisai, and M. Nakano. 2009. Potential physiological importance of pyrroloquinoline quinone. Alternative Medicine Review 14: 268–277.PubMed Rucker, R., W. Chowanadisai, and M. Nakano. 2009. Potential physiological importance of pyrroloquinoline quinone. Alternative Medicine Review 14: 268–277.PubMed
21.
go back to reference Lee, Y.R., J.K. Hwang, H.S. Lee, Y.J. Cheon, J.H. Ryu, S.I. Lee, H.B. Kwak, S.M. Lee, J.S. Kim, J.W. Park, R. Jeon, and B.H. Park. 2011. SPA0355, a thiourea analogue, inhibits inflammatory responses and joint destruction in fibroblast-like synoviocytes and mice with collagen-induced arthritis. British Journal of Pharmacology 164: 794–806.PubMedCentralCrossRefPubMed Lee, Y.R., J.K. Hwang, H.S. Lee, Y.J. Cheon, J.H. Ryu, S.I. Lee, H.B. Kwak, S.M. Lee, J.S. Kim, J.W. Park, R. Jeon, and B.H. Park. 2011. SPA0355, a thiourea analogue, inhibits inflammatory responses and joint destruction in fibroblast-like synoviocytes and mice with collagen-induced arthritis. British Journal of Pharmacology 164: 794–806.PubMedCentralCrossRefPubMed
22.
go back to reference Choi, Y.J., W.S. Lee, E.G. Lee, M.S. Sung, and W.H. Yoo. 2014. Sulforaphane inhibits IL-1beta-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of MMPs, COX-2, and PGE2. Inflammation 37: 1496–1503.CrossRefPubMed Choi, Y.J., W.S. Lee, E.G. Lee, M.S. Sung, and W.H. Yoo. 2014. Sulforaphane inhibits IL-1beta-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of MMPs, COX-2, and PGE2. Inflammation 37: 1496–1503.CrossRefPubMed
23.
go back to reference Weyand, C.M. 2000. New insights into the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 39(Suppl 1): 3–8.CrossRef Weyand, C.M. 2000. New insights into the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 39(Suppl 1): 3–8.CrossRef
24.
go back to reference Yamanishi, Y., and G.S. Firestein. 2001. Pathogenesis of rheumatoid arthritis: The role of synoviocytes. Rheumatic Diseases Clinics of North America 27: 355–371.CrossRefPubMed Yamanishi, Y., and G.S. Firestein. 2001. Pathogenesis of rheumatoid arthritis: The role of synoviocytes. Rheumatic Diseases Clinics of North America 27: 355–371.CrossRefPubMed
25.
go back to reference Chen, Y., and D.L. Mattey. 2012. Age at onset of rheumatoid arthritis: Association with polymorphisms in the vascular endothelial growth factor A (VEGFA) gene and an intergenic locus between matrix metalloproteinase (MMP) 1 and 3 genes. Clinical and Experimental Rheumatology 30: 894–898.PubMed Chen, Y., and D.L. Mattey. 2012. Age at onset of rheumatoid arthritis: Association with polymorphisms in the vascular endothelial growth factor A (VEGFA) gene and an intergenic locus between matrix metalloproteinase (MMP) 1 and 3 genes. Clinical and Experimental Rheumatology 30: 894–898.PubMed
26.
go back to reference Tanaka, Y. 2001. The role of chemokines and adhesion molecules in the pathogenesis of rheumatoid arthritis. Drugs of Today (Barcelona, Spain) 37: 477–484.CrossRef Tanaka, Y. 2001. The role of chemokines and adhesion molecules in the pathogenesis of rheumatoid arthritis. Drugs of Today (Barcelona, Spain) 37: 477–484.CrossRef
27.
go back to reference Sommerfelt, R.M., A.J. Feuerherm, K. Jones, and B. Johansen. 2013. Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes. PLoS ONE 8, e83555.PubMedCentralCrossRefPubMed Sommerfelt, R.M., A.J. Feuerherm, K. Jones, and B. Johansen. 2013. Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes. PLoS ONE 8, e83555.PubMedCentralCrossRefPubMed
28.
go back to reference Visser, K., C. Smith, and A. Louw. 2010. Interplay of the inflammatory and stress systems in a hepatic cell line: Interactions between glucocorticoid receptor agonists and interleukin-6. Endocrinology 151: 5279–5293.CrossRefPubMed Visser, K., C. Smith, and A. Louw. 2010. Interplay of the inflammatory and stress systems in a hepatic cell line: Interactions between glucocorticoid receptor agonists and interleukin-6. Endocrinology 151: 5279–5293.CrossRefPubMed
29.
go back to reference Baillet, A., L. Gossec, S. Paternotte, A. Etcheto, B. Combe, O. Meyer, X. Mariette, J.E. Gottenberg, and M. Dougados. 2014. Evaluation of serum IL-6 level as a surrogate marker of synovial inflammation and as a factor of structural progression in early rheumatoid arthritis: Results from the ESPOIR cohort. Arthritis Care Res (Hoboken). Baillet, A., L. Gossec, S. Paternotte, A. Etcheto, B. Combe, O. Meyer, X. Mariette, J.E. Gottenberg, and M. Dougados. 2014. Evaluation of serum IL-6 level as a surrogate marker of synovial inflammation and as a factor of structural progression in early rheumatoid arthritis: Results from the ESPOIR cohort. Arthritis Care Res (Hoboken).
30.
go back to reference Lee, H.Y., H.S. Jeon, E.K. Song, M.K. Han, S.I. Park, S.I. Lee, H.J. Yun, J.R. Kim, J.S. Kim, Y.C. Lee, S.I. Kim, H.R. Kim, J.Y. Choi, I. Kang, H.Y. Kim, and W.H. Yoo. 2006. CD40 ligation of rheumatoid synovial fibroblasts regulates RANKL-mediated osteoclastogenesis: Evidence of NF-kappaB-dependent, CD40-mediated bone destruction in rheumatoid arthritis. Arthritis and Rheumatism 54: 1747–1758.CrossRefPubMed Lee, H.Y., H.S. Jeon, E.K. Song, M.K. Han, S.I. Park, S.I. Lee, H.J. Yun, J.R. Kim, J.S. Kim, Y.C. Lee, S.I. Kim, H.R. Kim, J.Y. Choi, I. Kang, H.Y. Kim, and W.H. Yoo. 2006. CD40 ligation of rheumatoid synovial fibroblasts regulates RANKL-mediated osteoclastogenesis: Evidence of NF-kappaB-dependent, CD40-mediated bone destruction in rheumatoid arthritis. Arthritis and Rheumatism 54: 1747–1758.CrossRefPubMed
31.
go back to reference Choy, E.H., and G.S. Panayi. 2001. Cytokine pathways and joint inflammation in rheumatoid arthritis. New England Journal of Medicine 344: 907–916.CrossRefPubMed Choy, E.H., and G.S. Panayi. 2001. Cytokine pathways and joint inflammation in rheumatoid arthritis. New England Journal of Medicine 344: 907–916.CrossRefPubMed
32.
go back to reference Verma, I.M., J.K. Stevenson, E.M. Schwarz, D. Van Antwerp, and S. Miyamoto. 1995. Rel/NF-kappa B/I kappa B family: Intimate tales of association and dissociation. Genes and Development 9: 2723–2735.CrossRefPubMed Verma, I.M., J.K. Stevenson, E.M. Schwarz, D. Van Antwerp, and S. Miyamoto. 1995. Rel/NF-kappa B/I kappa B family: Intimate tales of association and dissociation. Genes and Development 9: 2723–2735.CrossRefPubMed
33.
go back to reference Han, Z., D.L. Boyle, L. Chang, B. Bennett, M. Karin, L. Yang, A.M. Manning, and G.S. Firestein. 2001. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. Journal of Clinical Investigation 108: 73–81.PubMedCentralCrossRefPubMed Han, Z., D.L. Boyle, L. Chang, B. Bennett, M. Karin, L. Yang, A.M. Manning, and G.S. Firestein. 2001. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. Journal of Clinical Investigation 108: 73–81.PubMedCentralCrossRefPubMed
34.
go back to reference McIntyre, K.W., D.J. Shuster, K.M. Gillooly, D.M. Dambach, M.A. Pattoli, P. Lu, X.D. Zhou, Y. Qiu, F.C. Zusi, and J.R. Burke. 2003. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis and Rheumatism 48: 2652–2659.CrossRefPubMed McIntyre, K.W., D.J. Shuster, K.M. Gillooly, D.M. Dambach, M.A. Pattoli, P. Lu, X.D. Zhou, Y. Qiu, F.C. Zusi, and J.R. Burke. 2003. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis and Rheumatism 48: 2652–2659.CrossRefPubMed
35.
go back to reference Nishikawa, M., A. Myoui, T. Tomita, K. Takahi, A. Nampei, and H. Yoshikawa. 2003. Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis and Rheumatism 48: 2670–2681.CrossRefPubMed Nishikawa, M., A. Myoui, T. Tomita, K. Takahi, A. Nampei, and H. Yoshikawa. 2003. Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis and Rheumatism 48: 2670–2681.CrossRefPubMed
36.
go back to reference Karin, M., Y. Yamamoto, and Q.M. Wang. 2004. The IKK NF-kappa B system: A treasure trove for drug development. Nature Reviews Drug Discovery 3: 17–26.CrossRefPubMed Karin, M., Y. Yamamoto, and Q.M. Wang. 2004. The IKK NF-kappa B system: A treasure trove for drug development. Nature Reviews Drug Discovery 3: 17–26.CrossRefPubMed
37.
go back to reference Pascual, O., S. Ben Achour, P. Rostaing, A. Triller, and A. Bessis. 2012. Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proceedings of the National Academy of Sciences of the United States of America 109: E197–205.PubMedCentralCrossRefPubMed Pascual, O., S. Ben Achour, P. Rostaing, A. Triller, and A. Bessis. 2012. Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proceedings of the National Academy of Sciences of the United States of America 109: E197–205.PubMedCentralCrossRefPubMed
39.
go back to reference Perry, V.H., C. Cunningham, and C. Holmes. 2007. Systemic infections and inflammation affect chronic neurodegeneration. Nature Reviews Immunology 7: 161–167.CrossRefPubMed Perry, V.H., C. Cunningham, and C. Holmes. 2007. Systemic infections and inflammation affect chronic neurodegeneration. Nature Reviews Immunology 7: 161–167.CrossRefPubMed
40.
go back to reference Yang, C., L. Yu, L. Kong, R. Ma, J. Zhang, Q. Zhu, J. Zhu, and D. Hao. 2014. Pyrroloquinoline quinone (PQQ) inhibits lipopolysaccharide induced inflammation in part via downregulated NF-kappaB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice. PLoS ONE 9, e109502.PubMedCentralCrossRefPubMed Yang, C., L. Yu, L. Kong, R. Ma, J. Zhang, Q. Zhu, J. Zhu, and D. Hao. 2014. Pyrroloquinoline quinone (PQQ) inhibits lipopolysaccharide induced inflammation in part via downregulated NF-kappaB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice. PLoS ONE 9, e109502.PubMedCentralCrossRefPubMed
Metadata
Title
Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways
Authors
Zhongbing Liu
Chi Sun
Ran Tao
Xinbao Xu
Libin Xu
Hongbing Cheng
Youhua Wang
Dongmei Zhang
Publication date
01-02-2016
Publisher
Springer US
Published in
Inflammation / Issue 1/2016
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-015-0245-7

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