A REVIEW ON MACROPHAGES AND THE IMPACT OF PROTEASOME INHIBITORS ON RHEUMATOID ARTHRITIS

Authors

  • CHITRA SELVARAJAN Department of Biochemistry, New Prince Shri Bhavani Arts and Science College, Medavakkam, Chennai-100, India https://orcid.org/0000-0002-8920-6341
  • NALINI GANESAN Department of Biochemistry, Sri Ramachandra Institute of Higher Education and Research, Sri Ramachandra University, Porur, Chennai-116, India https://orcid.org/0000-0001-8663-0625

DOI:

https://doi.org/10.22159/ijpps.2024v16i5.50845

Keywords:

Monocytes, Macrophages, Rheumatoid arthritis, Proteasome inhibitor, Cytokine

Abstract

Rheumatoid Arthritis (RA) is a common autoimmune disease that causes chronic inflammation of the tissues around the joints, which eventually results in systemic complications and bone destruction. Macrophages are critical cells in many tissues and organs essential to an innate and adaptive immune response. It is one of the most common cell types in the synovium of rheumatoid arthritis.  Various conventional and experimental therapies for RA target proteins, cytokines or their synthetic pathways, T lymphocytes, and B lymphocytes. The Fibroblast-Like Synoviocytes (FLS) and macrophages are abundantly activated in RA, and the drugs targeting the monocytes and macrophages are explored significantly less. The drugs targeting monocytes and macrophages may provide a better therapeutic strategy for RA. Proteasome inhibitors act as a potential remedy for autoimmune and inflammatory diseases. Targeting the monocytes and macrophages with proteasome inhibitors may improve the therapeutic approaches to RA. This paper reviews the types and significance of macrophages in RA, various conventional and experimental therapy approaches targeting monocytes and macrophages, and the effect of proteasome inhibitors on macrophages in RA.

Downloads

Download data is not yet available.

References

Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SMH, Zakeri A, Alagheband Bahrami A. Recent advances in understanding the pathogenesis of rheumatoid arthritis: new treatment strategies. Cells. 2021 Nov 4;10(11):3017. doi: 10.3390/cells10113017, PMID 34831240, PMCID PMC8616543.

Ross EA, Devitt A, Johnson JR. Macrophages: the good, the bad, and the gluttony. Front Immunol. 2021 Aug 12;12:708186. doi: 10.3389/fimmu.2021.708186, PMID 34456917, PMCID PMC8397413.

Pap T, Dankbar B, Wehmeyer C, Korb-Pap A, Sherwood J. Synovial fibroblasts and articular tissue remodelling: role and mechanisms. Semin Cell Dev Biol. 2020 May;101:140-5. doi: 10.1016/j.semcdb.2019.12.006, PMID 31956018.

Tu J, Wang X, Gong X, Hong W, Han D, Fang Y. Synovial macrophages in rheumatoid arthritis: the past, present, and future. Mediators Inflamm. 2020 Apr 13;2020:1583647. doi: 10.1155/2020/1583647, PMID 32351318, PMCID PMC7174945.

Ingegnoli F, Coletto LA, Scotti I, Compagnoni R, Randelli PS, Caporali R. The crucial questions on synovial biopsy: when, why, who, what, where, and how? Front Med (Lausanne). 2021 Aug 6;8:705382. doi: 10.3389/fmed.2021.705382, PMID 34422862, PMCID PMC8377390.

Misra R, Sharma BL, Gupta R, Pandya S, Agarwal S, Agarwal P. Indian rheumatology association consensus statement on the management of adults with rheumatoid arthritis. Indian Journal of Rheumatology. 2008;3(3):S1-S16. doi: 10.1016/S0973-3698(10)60373-1.

Ross JA, Auger MJ. The biology of the macrophage. In: The macrophage. 2nd ed. Oxford Academic; 2002. p. 1-72. doi: 10.1093/oso/9780192631978.003.0001.

Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 2007 Apr;7(4):292-304. doi: 10.1038/nri2062, PMID 17380158.

Lee C, Jeong H, Bae Y, Shin K, Kang S, Kim H. Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide. J Immunother Cancer. 2019 Jun 7;7(1):147. doi: 10.1186/s40425-019-0610-4, PMID 31174610, PMCID PMC6555931.

Arora S, Dev K, Agarwal B, Das P, Syed MA. Macrophages: their role, activation and polarization in pulmonary diseases. Immunobiology. 2018 Apr-May;223(4-5):383-96. doi: 10.1016/j.imbio.2017.11.001, PMID 29146235, PMCID PMC7114886.

Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677-86. doi: 10.1016/j.it.2004.09.015. PMID 15530839.

Wang Y, Smith W, Hao D, He B, Kong L. M1 and M2 macrophage polarization and potentially therapeutic naturally occurring compounds. Int Immunopharmacol. 2019;70:459-66. doi: 10.1016/j.intimp.2019.02.050, PMID 30861466.

Jitta SR, Salwa BNA, Bhaskaran NA, Marques SM, Kumar L. Recent advances in nanoformulation development of ritonavir, a key protease inhibitor used in the treatment of HIV-AIDS. Expert Opin Drug Deliv. 2022 Sep;19(9):1133-48. doi: 10.1080/17425247.2022.2121817, PMID 36063032.

Klyachko NL, Polak R, Haney MJ, Zhao Y, Gomes Neto RJ, Hill MC. Macrophages with cellular backpacks for targeted drug delivery to the brain. Biomaterials. 2017 Sep;140:79-87. doi: 10.1016/j.biomaterials.2017.06.017, PMID 28633046, PMCID PMC5605925.

Ye ZP, Ai XL, Faramand AM, Fang F. Macrophages as nanocarriers for drug delivery: novel therapeutics for central nervous system diseases. J Nanosci Nanotechnol. 2018 Jan 1;18(1):471-85. doi: 10.1166/jnn.2018.15218, PMID 29768873.

Peng H, Xian D, Liu J, Pan S, Tang R, Zhong J. Regulating the polarization of macrophages: a promising approach to vascular dermatosis. J Immunol Res. 2020 Jul 28;2020:8148272. doi: 10.1155/2020/8148272, PMID 32775470, PMCID PMC7407038.

Huang Y, Guan Z, Dai X, Shen Y, Wei Q, Ren L. Engineered macrophages as near-infrared light-activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer. Nat Commun. 2021 Jul 14;12(1):4310. doi: 10.1038/s41467-021-24564-0, PMID 34262026, PMCID PMC8280231.

Oishi Y, Manabe I. Macrophages in inflammation, repair and regeneration. Int Immunol. 2018 Oct 29;30(11):511-28. doi: 10.1093/intimm/dxy054, PMID 30165385.

Watanabe S, Alexander M, Misharin AV, Budinger GRS. The role of macrophages in the resolution of inflammation. J Clin Invest. 2019 May 20;129(7):2619-28. doi: 10.1172/JCI124615, PMID 31107246, PMCID PMC6597225.

He W, Kapate N, Shields CW, Mitragotri S. Drug delivery to macrophages: a review of targeting drugs and drug carriers to macrophages for inflammatory diseases. Adv Drug Deliv Rev. 2020;165-166:15-40. doi: 10.1016/j.addr.2019.12.001, PMID 31816357.

Ross EA, Devitt A, Johnson JR. Macrophages: the good, the bad, and the gluttony. Front Immunol. 2021 Aug 12;12:708186. doi: 10.3389/fimmu.2021.708186, PMID 34456917, PMCID PMC8397413.

Zhu P, Ding J, Zhou J, Dong WJ, Fan CM, Chen ZN. Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production. Arthritis Res Ther. 2005;7(5):R1023-33. doi: 10.1186/ar1778, PMID 16207318, PMCID PMC1257431.

Kinne RW, Stuhlmüller B, Burmester GR. Cells of the synovium in rheumatoid arthritis. Macrophages Arthritis Res Ther. 2007;9(6):224. doi: 10.1186/ar2333, PMID 18177511, PMCID PMC2246244.

Arora T, Padaki R, Liu L, Hamburger AE, Ellison AR, Stevens SR. Differences in binding and effector functions between classes of TNF antagonists. Cytokine. 2009 Feb;45(2):124-31. doi: 10.1016/j.cyto.2008.11.008, PMID 19128982.

Hocaoglu C, Kural B, Aliyazıcıoglu R, Deger O, Cengiz S. IL-1β, IL-6, IL-8, IL-10, IFN-γ, TNF-α and its relationship with lipid parameters in patients with major depression. Metab Brain Dis. 2012 Dec;27(4):425-30. doi: 10.1007/s11011-012-9323-9, PMID 22707092.

Chung ES, Chauhan SK, Jin Y, Nakao S, Hafezi Moghadam A, Van Rooijen N. Contribution of macrophages to angiogenesis induced by vascular endothelial growth factor receptor-3-specific ligands. Am J Pathol. 2009 Nov;175(5):1984-92. doi: 10.2353/ajpath.2009.080515, PMID 19808642, PMCID PMC2774062.

Guo X, Chen G. Hypoxia-inducible factor is critical for pathogenesis and regulation of immune cell functions in rheumatoid arthritis. Front Immunol. 2020 Jul 28;11:1668. doi: 10.3389/fimmu.2020.01668, PMID 32849577, PMCID PMC7399093.

Szekanecz Z, Besenyei T, Paragh G, Koch AE. New insights in synovial angiogenesis. Joint Bone Spine. 2010 Jan;77(1):13-9. doi: 10.1016/j.jbspin.2009.05.011, PMID 20022538, PMCID PMC2910514.

Parihar A, Eubank TD, Doseff AI. Monocytes and macrophages regulate immunity through dynamic networks of survival and cell death. J Innate Immun. 2010;2(3):204-15. doi: 10.1159/000296507, PMID 20375558, PMCID PMC2956013.

Modi S, Soejima M, Levesque MC. The effect of targeted rheumatoid arthritis therapies on anti-citrullinated protein autoantibody levels and B cell responses. Clin Exp Immunol. 2013 Jul;173(1):8-17. doi: 10.1111/cei.12114, PMID 23607804, PMCID PMC3694530.

Jang CH, Choi JH, Byun MS, Jue DM. Chloroquine inhibits the production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatol (Oxf Engl). 2006 Jun;45(6):703-10. doi: 10.1093/rheumatology/kei282. PMID 16418198.

Suzuki E, Umezawa K. Inhibition of macrophage activation and phagocytosis by a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin. Biomed Pharmacother. 2006 Nov;60(9):578-86. doi: 10.1016/j.biopha.2006.07.089, PMID 16978829.

Richards PJ, Williams AS, Goodfellow RM, Williams BD. Liposomal clodronate eliminates synovial macrophages, reduces inflammation and ameliorates joint destruction in antigen-induced arthritis. Rheumatol (Oxf Engl). 1999 Sep;38(9):818-25. doi: 10.1093/rheumatology/38.9.818, PMID 10515641.

Qureshi AA, Tan X, Reis JC, Badr MZ, Papasian CJ, Morrison DC. Suppression of nitric oxide induction and pro-inflammatory cytokines by novel proteasome inhibitors in various experimental models. Lipids Health Dis. 2011 Oct 12;10:177. doi: 10.1186/1476-511X-10-177, PMID 21992595, PMCID PMC3206449.

Miagkov AV, Kovalenko DV, Brown CE, Didsbury JR, Cogswell JP, Stimpson SA. NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc Natl Acad Sci USA. 1998 Nov 10;95(23):13859-64. doi: 10.1073/pnas.95.23.13859, PMID 9811891, PMCID PMC24931.

Miller CP, Ban K, Dujka ME, McConkey DJ, Munsell M, Palladino M. NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood. 2007 Jul 1;110(1):267-77. doi: 10.1182/blood-2006-03-013128, PMID 17356134, PMCID PMC1896116.

Brun J. Proteasome inhibition as a novel therapy in treating rheumatoid arthritis. Med Hypotheses. 2008;71(1):65-72. doi: 10.1016/j.mehy.2008.02.014, PMID 18424014.

Van der Heijden JW, Oerlemans R, Lems WF, Scheper RJ, Dijkmans BA, Jansen G. The proteasome inhibitor bortezomib inhibits the release of NFkappaB-inducible cytokines and induces apoptosis of activated T cells from rheumatoid arthritis patients. Clin Exp Rheumatol. 2009 Jan-Feb;27(1):92-8. PMID 19327235.

Yannaki E, Papadopoulou A, Athanasiou E, Kaloyannidis P, Paraskeva A, Bougiouklis D. The proteasome inhibitor bortezomib drastically affects inflammation and bone disease in adjuvant-induced arthritis in rats. Arthritis Rheum. 2010 Nov;62(11):3277-88. doi: 10.1002/art.27690, PMID 20722034.

Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J. 1991 Dec;10(13):4025-31. doi: 10.1002/j.1460-2075.1991.tb04978.x, PMID 1721867, PMCID PMC453150.

Williams RO, Feldmann M, Maini RN. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci USA. 1992 Oct 15;89(20):9784-8. doi: 10.1073/pnas.89.20.9784, PMID 1409699, PMCID PMC50217.

Schadlich H, Ermann J, Biskop M, Falk W, Sperling F, Jungel A. Anti-inflammatory effects of systemic anti-tumour necrosis factor alpha treatment in human/murine SCID arthritis. Ann Rheum Dis. 1999 Jul;58(7):428-34. doi: 10.1136/ard.58.7.428, PMID 10381487, PMCID PMC1752912.

Tak PP, Gerlag DM, Aupperle KR, van de Geest DA, Overbeek M, Bennett BL. Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Arthritis Rheum. 2001 Aug;44(8):1897-907. doi: 10.1002/1529-0131(200108)44:8<1897::AID-ART328>3.0.CO;2-4, PMID 11508443.

Bozec A, Zaiss MM, Kagwiria R, Voll R, Rauh M, Chen Z. T cell costimulation molecules CD80/86 inhibit osteoclast differentiation by inducing the IDO/tryptophan pathway. Sci Transl Med. 2014 May 7;6(235):235ra60. doi: 10.1126/scitranslmed.3007764, PMID 24807557.

Durie FH, Fava RA, Foy TM, Aruffo A, Ledbetter JA, Noelle RJ. Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. Science. 1993 Sep 3;261(5126):1328-30. doi: 10.1126/science.7689748, PMID 7689748.

Andreakos E, Rauchhaus U, Stavropoulos A, Endert G, Wendisch V, Benahmed AS. Amphoteric liposomes enable systemic antigen-presenting cell-directed delivery of CD40 antisense and are therapeutically effective in experimental arthritis. Arthritis Rheum. 2009 Apr;60(4):994-1005. doi: 10.1002/art.24434, PMID 19333921.

Pine PR, Chang B, Schoettler N, Banquerigo ML, Wang S, Lau A. Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. Clin Immunol. 2007 Sep;124(3):244-57. doi: 10.1016/j.clim.2007.03.543, PMID 17537677.

Wang L, Liu L, Hong X, Liu D, Cheng Z. Delanzomib, a novel proteasome inhibitor, combined with adalimumab drastically ameliorates collagen-induced arthritis in rats by improving and prolonging the Anti-TNF-α effect of adalimumab. Front Pharmacol. 2021 Nov 22;12:782385. doi: 10.3389/fphar.2021.782385, PMID 34880764, PMCID PMC8645831.

Selvarajan C, Ganesan N, T Srinivasan L, Gopalakrishnan R. The effect of proteasome inhibitor (AM114) on apoptosis in IL-1β-treated peripheral blood macrophage cultured cells from rheumatoid arthritis patients. Indian J Rheumatol. 2016;11(1):7-13. doi: 10.1016/j.injr.2015.10.005.

Malode A, Yadav RN, Goyal GG, Jain G, Mathur A, Goyal L. Pulmonary function in rheumatoid arthrits: a cross-sectional study. Int J Curr Pharm Sci. 2024;16(2):120-3. doi: 10.22159/ijcpr.2024v16i2.4057.

Pasam Jyothirmayi, Devalarao G, Mandava Venkata Basaveswara Rao. Formulation and evaluation of modified oral chronotropic drug delivery systems of tramadol hydrochloride for rheumatoid arthritis pain. Asian J Pharm Clin Res. 2019;12:120-6. doi: 10.22159/ajpcr.2019.v12i7.32992.

Davignon JL, Hayder M, Baron M, Boyer JF, Constantin A, Apparailly F. Targeting monocytes/macrophages in the treatment of rheumatoid arthritis. Rheumatol (Oxf Engl). 2013 Apr;52(4):590-8. doi: 10.1093/rheumatology/kes304, PMID 23204551.

Barrera P, Blom A, van Lent PL, van Bloois L, Beijnen JH, van Rooijen N. Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis. Arthritis Rheum. 2000 Sep;43(9):1951-9. doi: 10.1002/1529-0131(200009)43:9<1951::AID-ANR5>3.0.CO;2-K, PMID 11014344.

Hu Y, Wang B, Shen J, Low SA, Putt KS, Niessen HWM. Depletion of activated macrophages with a folate receptor-beta-specific antibody improves symptoms in mouse models of rheumatoid arthritis. Arthritis Res Ther. 2019 Jun 7;21(1):143. doi: 10.1186/s13075-019-1912-0, PMID 31174578, PMCID PMC6555977.

Kirdaite G, Lange N, Busso N, Van Den Bergh H, Kucera P, So A. Protoporphyrin IX photodynamic therapy for synovitis. Arthritis Rheum. 2002 May;46(5):1371-8. doi: 10.1002/art.10199, PMID 12115245.

Wos I, Tabarkiewicz J. Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis. Immunol Res. 2021 Feb;69(1):26-42. doi: 10.1007/s12026-021-09173-9, PMID 33515210, PMCID PMC7921069.

Westra J, Doornbos-van der Meer B, de Boer P, van Leeuwen MA, van Rijswijk MH, Limburg PC. Strong inhibition of TNF-alpha production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Arthritis Res Ther. 2004;6(4):R384-92. doi: 10.1186/ar1204, PMID 15225374, PMCID PMC464924.

Feldmann M, Andreakos E, Smith C, Bondeson J, Yoshimura S, Kiriakidis S. Is NF-kappaB a useful therapeutic target in rheumatoid arthritis? Ann Rheum Dis. 2002 Nov;61Suppl 2:ii13-8. doi: 10.1136/ard.61.suppl_2.ii13[Suppl], PMID 12379614, PMCID PMC1766706.

Khalesi N, Korani S, Korani M, Johnston TP, Sahebkar A. Bortezomib: a proteasome inhibitor for the treatment of autoimmune diseases. Inflammopharmacology. 2021 Oct;29(5):1291-306. doi: 10.1007/s10787-021-00863-2, PMID 34424482.

Wang J, Wang Y, He S, Wang Z, Deng Q, Liang H. Proteasome inhibition induces macrophage apoptosis via mitochondrial dysfunction. J Biochem Mol Toxicol. 2021 Nov;35(11):e22894. doi: 10.1002/jbt.22894, PMID 34418242.

Chitra S, Nalini G, Rajasekhar G. The ubiquitin-proteasome system and efficacy of proteasome inhibitors in diseases. Int J Rheum Dis. 2012 Jun;15(3):249-60. doi: 10.1111/j.1756-185X.2012.01737.x, PMID 22709487.

Published

01-05-2024

How to Cite

SELVARAJAN, C., and N. GANESAN. “A REVIEW ON MACROPHAGES AND THE IMPACT OF PROTEASOME INHIBITORS ON RHEUMATOID ARTHRITIS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 16, no. 5, May 2024, pp. 48-53, doi:10.22159/ijpps.2024v16i5.50845.

Issue

Section

Review Article(s)