Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis–NETosis Balance of Neutrophils
Abstract
:1. Introduction
2. Results
2.1. AD Ameliorated Adjuvant-Induced Arthritis (AA) in Mice
2.2. AD Decreases Neutrophils Infiltration
2.3. AD Accelerates Neutrophil Apoptosis in the Presence of LPS
2.4. AD Inhibited PMA-Induced NETosis
2.5. AD Inhibited Neutrophil Autophagy
3. Discussion
4. Materials and Methods
4.1. Reagents and Antibodies
4.2. Animals
4.3. Induction of Adjuvant-Induced Arthritis (AA)
4.4. Histochemistry and Immunohistochemistry
4.5. Cytokine Analysis
4.6. Air Pouch Experiments
4.7. Isolation of Mouse Neutrophils and Culture
4.8. Western Blot Analysis
4.9. Immunofluorescence Assay
4.10. Flow Cytometry Analysis
4.11. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- McInnes, I.B.; Schett, G. The pathogenesis of rheumatoid arthritis. N Engl J. Med. 2011, 365, 2205–2219. [Google Scholar] [CrossRef] [PubMed]
- Smolen, J.S.; Aletaha, D.; McInnes, I.B. Rheumatoid arthritis. Lancet 2016, 388, 2023–2038. [Google Scholar] [CrossRef]
- Wright, H.L.; Moots, R.J.; Edwards, S.W. The multifactorial role of neutrophils in rheumatoid arthritis. Nat. Rev. Rheumatol. 2014, 10, 593–601. [Google Scholar] [CrossRef] [PubMed]
- Thieblemont, N.; Wright, H.L.; Edwards, S.W.; Witko-Sarsat, V. Human neutrophils in auto-immunity. Semin. Immunol. 2016, 28, 159–173. [Google Scholar] [CrossRef] [PubMed]
- Cecchi, I.; Arias de la Rosa, I.; Menegatti, E.; Roccatello, D.; Collantes-Estevez, E.; Lopez-Pedrera, C.; Barbarroja, N. Neutrophils: Novel key players in Rheumatoid Arthritis. Current and future therapeutic targets. Autoimmun. Rev. 2018, 17, 1138–1149. [Google Scholar] [CrossRef] [PubMed]
- Lefrancais, E.; Roga, S.; Gautier, V.; Gonzalez-de-Peredo, A.; Monsarrat, B.; Girard, J.P.; Cayrol, C. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc. Natl. Acad. Sci. USA 2012, 109, 1673–1678. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brinkmann, V.; Reichard, U.; Goosmann, C.; Fauler, B.; Uhlemann, Y.; Weiss, D.S.; Weinrauch, Y.; Zychlinsky, A. Neutrophil extracellular traps kill bacteria. Science 2004, 303, 1532–1535. [Google Scholar] [CrossRef] [PubMed]
- Khandpur, R.; Carmona-Rivera, C.; Vivekanandan-Giri, A.; Gizinski, A.; Yalavarthi, S.; Knight, J.S.; Friday, S.; Li, S.; Patel, R.M.; Subramanian, V.; et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci. Transl. Med. 2013, 5, 178ra40. [Google Scholar] [CrossRef] [PubMed]
- Chakravarti, A.; Raquil, M.A.; Tessier, P.; Poubelle, P.E. Surface RANKL of Toll-like receptor 4-stimulated human neutrophils activates osteoclastic bone resorption. Blood 2009, 114, 1633–1644. [Google Scholar] [CrossRef] [PubMed]
- Chen, W.; Wang, Q.; Ke, Y.; Lin, J. Neutrophil Function in an Inflammatory Milieu of Rheumatoid Arthritis. J. Immunol. Res. 2018, 2018, 8549329. [Google Scholar] [CrossRef]
- Kaplan, M.J. Role of neutrophils in systemic autoimmune diseases. Arthritis Res. Ther. 2013, 15, 219. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, D.; Kagari, T.; Doi, H.; Shimozato, T. Essential role of neutrophils in anti-type II collagen antibody and lipopolysaccharide-induced arthritis. Immunology 2006, 119, 195–202. [Google Scholar] [CrossRef] [PubMed]
- Smolen, J.S.; Kay, J.; Doyle, M.K.; Landewe, R.; Matteson, E.L.; Wollenhaupt, J.; Gaylis, N.; Murphy, F.T.; Neal, J.S.; Zhou, Y.; et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): A multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 2009, 374, 210–221. [Google Scholar] [CrossRef]
- Van Vollenhoven, R.F.; Fleischmann, R.; Cohen, S.; Lee, E.B.; Garcia Meijide, J.A.; Wagner, S.; Forejtova, S.; Zwillich, S.H.; Gruben, D.; Koncz, T.; et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl. J. Med. 2012, 367, 508–519. [Google Scholar] [CrossRef] [PubMed]
- Smolen, J.S.; Beaulieu, A.; Rubbert-Roth, A.; Ramos-Remus, C.; Rovensky, J.; Alecock, E.; Woodworth, T.; Alten, R.; Investigators, O. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): A double-blind, placebo-controlled, randomised trial. Lancet 2008, 371, 987–997. [Google Scholar] [CrossRef]
- Handa, S.S.; Sharma, A. Hepatoprotective activity of andrographolide against galactosamine & paracetamol intoxication in rats. Indian J. Med. Res. 1990, 92, 284–292. [Google Scholar]
- Sheeja, K.; Guruvayoorappan, C.; Kuttan, G. Antiangiogenic activity of Andrographis paniculata extract and andrographolide. Int. Immunopharmacol. 2007, 7, 211–221. [Google Scholar] [CrossRef]
- Thisoda, P.; Rangkadilok, N.; Pholphana, N.; Worasuttayangkurn, L.; Ruchirawat, S.; Satayavivad, J. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation. Eur. J. Pharmacol. 2006, 553, 39–45. [Google Scholar] [CrossRef]
- Hidalgo, M.A.; Romero, A.; Figueroa, J.; Cortes, P.; Concha, II; Hancke, J.L.; Burgos, R.A. Andrographolide interferes with binding of nuclear factor-kappaB to DNA in HL-60-derived neutrophilic cells. Br. J. Pharmacol. 2005, 144, 680–686. [Google Scholar] [CrossRef]
- Li, Z.Z.; Tan, J.P.; Wang, L.L.; Li, Q.H. Andrographolide Benefits Rheumatoid Arthritis via Inhibiting MAPK Pathways. Inflammation 2017, 40, 1599–1605. [Google Scholar] [CrossRef]
- Gupta, S.; Mishra, K.P.; Singh, S.B.; Ganju, L. Inhibitory effects of andrographolide on activated macrophages and adjuvant-induced arthritis. Inflammopharmacology 2018, 26, 447–456. [Google Scholar] [CrossRef] [PubMed]
- Zhai, Z.J.; Li, H.W.; Liu, G.W.; Qu, X.H.; Tian, B.; Yan, W.; Lin, Z.; Tang, T.T.; Qin, A.; Dai, K.R. Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo. Br. J. Pharmacol. 2014, 171, 663–675. [Google Scholar] [CrossRef]
- Yan, J.; Chen, Y.; He, C.; Yang, Z.Z.; Lu, C.; Chen, X.S. Andrographolide induces cell cycle arrest and apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes. Cell Biol. Toxicol. 2012, 28, 47–56. [Google Scholar] [CrossRef] [PubMed]
- Shen, Y.C.; Chen, C.F.; Chiou, W.F. Andrographolide prevents oxygen radical production by human neutrophils: Possible mechanism(s) involved in its anti-inflammatory effect. Br. J. Pharmacol. 2002, 135, 399–406. [Google Scholar] [CrossRef] [PubMed]
- Ng, L.G.; Ostuni, R.; Hidalgo, A. Heterogeneity of neutrophils. Nat. Rev. Immunol. 2019, 19, 255–265. [Google Scholar] [CrossRef] [PubMed]
- Collison, J. Rheumatoid arthritis: Tipping the balance towards resolution. Nat. Rev. Rheumatol. 2016, 12, 622. [Google Scholar] [CrossRef] [PubMed]
- Smolen, J.S.; Aletaha, D.; Barton, A.; Burmester, G.R.; Emery, P.; Firestein, G.S.; Kavanaugh, A.; McInnes, I.B.; Solomon, D.H.; Strand, V.; et al. Rheumatoid arthritis. Nat. Rev. Dis. Primers 2018, 4, 18001. [Google Scholar] [CrossRef]
- Yousefi, S.; Gold, J.A.; Andina, N.; Lee, J.J.; Kelly, A.M.; Kozlowski, E.; Schmid, I.; Straumann, A.; Reichenbach, J.; Gleich, G.J.; et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat. Med. 2008, 14, 949–953. [Google Scholar] [CrossRef]
- Boeltz, S.; Amini, P.; Anders, H.J.; Andrade, F.; Bilyy, R.; Chatfield, S.; Cichon, I.; Clancy, D.M.; Desai, J.; Dumych, T.; et al. To NET or not to NET: Current opinions and state of the science regarding the formation of neutrophil extracellular traps. Cell Death Differ. 2019, 26, 395–408. [Google Scholar] [CrossRef]
- Papayannopoulos, V. Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol. 2018, 18, 134–147. [Google Scholar] [CrossRef]
- Aleyd, E.; Al, M.; Tuk, C.W.; van der Laken, C.J.; van Egmond, M. IgA Complexes in Plasma and Synovial Fluid of Patients with Rheumatoid Arthritis Induce Neutrophil Extracellular Traps via FcalphaRI. J. Immunol. 2016, 197, 4552–4559. [Google Scholar] [CrossRef] [PubMed]
- Demoruelle, M.K.; Harrall, K.K.; Ho, L.; Purmalek, M.M.; Seto, N.L.; Rothfuss, H.M.; Weisman, M.H.; Solomon, J.J.; Fischer, A.; Okamoto, Y.; et al. Anti-Citrullinated Protein Antibodies Are Associated With Neutrophil Extracellular Traps in the Sputum in Relatives of Rheumatoid Arthritis Patients. Arthritis Rheumatol. 2017, 69, 1165–1175. [Google Scholar] [CrossRef] [PubMed]
- Harris, M.L.; Darrah, E.; Lam, G.K.; Bartlett, S.J.; Giles, J.T.; Grant, A.V.; Gao, P.; Scott, W.W., Jr.; El-Gabalawy, H.; Casciola-Rosen, L.; et al. Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis. Arthritis Rheum. 2008, 58, 1958–1967. [Google Scholar] [CrossRef] [PubMed]
- Halvorsen, E.H.; Pollmann, S.; Gilboe, I.M.; van der Heijde, D.; Landewe, R.; Odegard, S.; Kvien, T.K.; Molberg, O. Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associations with disease severity. Ann. Rheum. Dis. 2008, 67, 414–417. [Google Scholar] [CrossRef] [PubMed]
- Reyes-Castillo, Z.; Munoz-Valle, J.F.; Llamas-Covarrubias, M.A. Clinical and immunological aspects of anti-peptidylarginine deiminase type 4 (anti-PAD4) autoantibodies in rheumatoid arthritis. Autoimmun. Rev. 2018, 17, 94–102. [Google Scholar] [CrossRef] [PubMed]
- Doherty, J.; Baehrecke, E.H. Life, death and autophagy. Nat. Cell Biol. 2018, 20, 1110–1117. [Google Scholar] [CrossRef] [PubMed]
- Remijsen, Q.; Vanden Berghe, T.; Wirawan, E.; Asselbergh, B.; Parthoens, E.; De Rycke, R.; Noppen, S.; Delforge, M.; Willems, J.; Vandenabeele, P. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res. 2011, 21, 290–304. [Google Scholar] [CrossRef] [PubMed]
- Bhattacharya, A.; Wei, Q.; Shin, J.N.; Abdel Fattah, E.; Bonilla, D.L.; Xiang, Q.; Eissa, N.T. Autophagy Is Required for Neutrophil-Mediated Inflammation. Cell Rep. 2015, 12, 1731–1739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Park, S.Y.; Shrestha, S.; Youn, Y.J.; Kim, J.K.; Kim, S.Y.; Kim, H.J.; Park, S.H.; Ahn, W.G.; Kim, S.; Lee, M.G.; et al. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis. Am. J. Respir. Crit. Care Med. 2017, 196, 577–589. [Google Scholar] [CrossRef]
- Chen, Y.M.; Chang, C.Y.; Chen, H.H.; Hsieh, C.W.; Tang, K.T.; Yang, M.C.; Lan, J.L.; Chen, D.Y. Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy. Arthritis Res. Ther. 2018, 20, 268. [Google Scholar] [CrossRef]
- Dai, Y.; Ding, J.; Yin, W.; He, Y.; Yu, F.; Ye, C.; Hu, S.; Yu, Y. Increased Autophagy Enhances the Resistance to Tumor Necrosis Factor-Alpha Treatment in Rheumatoid Arthritis Human Fibroblast-Like Synovial Cell. Biomed. Res. Int. 2018, 2018, 4941027. [Google Scholar] [CrossRef] [PubMed]
- Catrina, A.I.; Svensson, C.I.; Malmstrom, V.; Schett, G.; Klareskog, L. Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis. Nat. Rev. Rheumatol. 2017, 13, 79–86. [Google Scholar] [CrossRef] [PubMed]
- Dewas, C.; Dang, P.M.; Gougerot-Pocidalo, M.A.; El-Benna, J. TNF-alpha induces phosphorylation of p47(phox) in human neutrophils: partial phosphorylation of p47phox is a common event of priming of human neutrophils by TNF-alpha and granulocyte-macrophage colony-stimulating factor. J. Immunol. 2003, 171, 4392–4398. [Google Scholar] [CrossRef] [PubMed]
- Cross, A.; Moots, R.J.; Edwards, S.W. The dual effects of TNFalpha on neutrophil apoptosis are mediated via differential effects on expression of Mcl-1 and Bfl-1. Blood 2008, 111, 878–884. [Google Scholar] [CrossRef] [PubMed]
- Amarilyo, G.; Lourenco, E.V.; Shi, F.D.; La Cava, A. IL-17 promotes murine lupus. J. Immunol. 2014, 193, 540–543. [Google Scholar] [CrossRef] [PubMed]
- McInnes, I.B.; Buckley, C.D.; Isaacs, J.D. Cytokines in rheumatoid arthritis - shaping the immunological landscape. Nat. Rev. Rheumatol. 2016, 12, 63–68. [Google Scholar] [CrossRef]
- Taylor, P.R.; Roy, S.; Leal, S.M., Jr.; Sun, Y.; Howell, S.J.; Cobb, B.A.; Li, X.; Pearlman, E. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORgammat and dectin-2. Nat. Immunol. 2014, 15, 143–151. [Google Scholar] [CrossRef]
- Lubberts, E.; Koenders, M.I.; van den Berg, W.B. The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res. Ther. 2005, 7, 29–37. [Google Scholar] [CrossRef]
- Burska, A.; Boissinot, M.; Ponchel, F. Cytokines as biomarkers in rheumatoid arthritis. Mediators Inflamm. 2014, 2014, 545493. [Google Scholar] [CrossRef]
- Kokkonen, H.; Soderstrom, I.; Rocklov, J.; Hallmans, G.; Lejon, K.; Rantapaa Dahlqvist, S. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 2010, 62, 383–391. [Google Scholar] [CrossRef]
- Ouyang, W.; Rutz, S.; Crellin, N.K.; Valdez, P.A.; Hymowitz, S.G. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu. Rev. Immunol. 2011, 29, 71–109. [Google Scholar] [CrossRef] [PubMed]
- Kulkarni, U.; Karsten, C.M.; Kohler, T.; Hammerschmidt, S.; Bommert, K.; Tiburzy, B.; Meng, L.; Thieme, L.; Recke, A.; Ludwig, R.J.; et al. IL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration. J. Allergy Clin. Immunol. 2016, 137, 1487–1497.e6. [Google Scholar] [CrossRef] [PubMed]
- Siebert, S.; Tsoukas, A.; Robertson, J.; McInnes, I. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol. Rev. 2015, 67, 280–309. [Google Scholar] [CrossRef] [PubMed]
- Liew, P.X.; Kubes, P. The Neutrophil’s Role During Health and Disease. Physiol. Rev. 2019, 99, 1223–1248. [Google Scholar] [CrossRef] [PubMed]
- Deng, X.; Ruvolo, P.; Carr, B.; May, W.S., Jr. Survival function of ERK1/2 as IL-3-activated, staurosporine-resistant Bcl2 kinases. Proc. Natl. Acad. Sci. USA 2000, 97, 1578–1583. [Google Scholar] [CrossRef] [Green Version]
- Perez-Sanchez, C.; Ruiz-Limon, P.; Aguirre, M.A.; Jimenez-Gomez, Y.; Arias-de la Rosa, I.; Abalos-Aguilera, M.C.; Rodriguez-Ariza, A.; Castro-Villegas, M.C.; Ortega-Castro, R.; Segui, P.; et al. Diagnostic potential of NETosis-derived products for disease activity, atherosclerosis and therapeutic effectiveness in Rheumatoid Arthritis patients. J. Autoimmun. 2017, 82, 31–40. [Google Scholar] [CrossRef]
- Koushik, S.; Joshi, N.; Nagaraju, S.; Mahmood, S.; Mudeenahally, K.; Padmavathy, R.; Jegatheesan, S.K.; Mullangi, R.; Rajagopal, S. PAD4: pathophysiology, current therapeutics and future perspective in rheumatoid arthritis. Expert. Opin. Ther. Targets 2017, 21, 433–447. [Google Scholar] [CrossRef]
- Turunen, S.; Huhtakangas, J.; Nousiainen, T.; Valkealahti, M.; Melkko, J.; Risteli, J.; Lehenkari, P. Rheumatoid arthritis antigens homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2, 3 and 4 in rheumatoid nodule and synovial tissue. Arthritis Res. Ther. 2016, 18, 239. [Google Scholar] [CrossRef]
- Guo, D.; Ma, J.; Yan, L.; Li, T.; Li, Z.; Han, X.; Shui, S. Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke. Cell Physiol. Biochem. 2017, 43, 182–194. [Google Scholar] [CrossRef]
- Matsumoto, G.; Wada, K.; Okuno, M.; Kurosawa, M.; Nukina, N. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol. Cell 2011, 44, 279–289. [Google Scholar] [CrossRef]
- Ilatovskaya, D.V.; Pavlov, T.S.; Levchenko, V.; Staruschenko, A. ROS production as a common mechanism of ENaC regulation by EGF, insulin, and IGF-1. Am. J. Physiol. Cell Physiol. 2013, 304, C102–C111. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guan, J.J.; Zhang, X.D.; Sun, W.; Qi, L.; Wu, J.C.; Qin, Z.H. DRAM1 regulates apoptosis through increasing protein levels and lysosomal localization of BAX. Cell Death Dis. 2015, 6, e1624. [Google Scholar] [CrossRef] [PubMed]
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Li, X.; Yuan, K.; Zhu, Q.; Lu, Q.; Jiang, H.; Zhu, M.; Huang, G.; Xu, A. Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis–NETosis Balance of Neutrophils. Int. J. Mol. Sci. 2019, 20, 5035. https://doi.org/10.3390/ijms20205035
Li X, Yuan K, Zhu Q, Lu Q, Jiang H, Zhu M, Huang G, Xu A. Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis–NETosis Balance of Neutrophils. International Journal of Molecular Sciences. 2019; 20(20):5035. https://doi.org/10.3390/ijms20205035
Chicago/Turabian StyleLi, Xiaohong, Kai Yuan, Qingqing Zhu, Qingyi Lu, Haixu Jiang, Mengmeng Zhu, Guangrui Huang, and Anlong Xu. 2019. "Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis–NETosis Balance of Neutrophils" International Journal of Molecular Sciences 20, no. 20: 5035. https://doi.org/10.3390/ijms20205035