Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker 3.8)
Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 11, November, p. 1491–1497

doi: 10.17219/acem/75611

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

The effect of caveolin-1 knockdown on interleukin-1β-induced chemokine (C-C motif) ligand 2 expression in synovial fluid-derived fibroblast-like synoviocytes from patients with rheumatoid arthritis

Dorota Trzybulska1,A,B,C,D,E,F, Anna Olewicz-Gawlik2,A,C,D,E,F, Jan Sikora3,C,D,E,F, Magdalena Frydrychowicz3,B,C,D,E,F, Agata Kolecka-Bednarczyk3,A,C,E,F, Mariusz Kaczmarek3,C,E,F, Pawel Hrycaj3,4,A,C,D,E,F

1 Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poland

2 Department of Infectious Diseases, Poznan University of Medical Sciences, Poland

3 Department of Immunology, Poznan University of Medical Sciences, Poland

4 Department of Rheumatology, Municipal Hospital, Kościan, Poland

Abstract

Background. Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destructive changes in peripheral joints and their irreversible deformity. The influx of chemoattractant-mediated inflammatory cells to the joints is one of the main features of RA.
Objectives. The aim of this study was to investigate the effect of a knockdown of caveolin-1 (CAV1), a known regulator of multiple cell signaling pathways, on chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) expression in synovial fluid-derived fibroblast-like synoviocytes (sfd-FLSs) obtained from patients with RA.
Material and Methods. Primary cell cultures of sfd-FLSs were established from RA synovial fluids. Cells were transiently transfected with small interfering RNA (siRNA) specific for CAV1, and then incubated with interleukin (IL)-1β to induce CCL2 expression. The expression levels of CAV1 and CCL2 were assessed at transcript level, using quantitative polymerase chain reaction (qPCR) and at protein level by enzyme-linked immunosorbent assay (ELISA) and western blotting analysis.
Results. A transient CAV1 knockdown in sfd-FLSs resulted in a decrease in the IL-1β-induced CCL2 mRNA expression level vs non-transfected cells and cells transfected with non-targeting siRNA. The concentration of secreted CCL2 was not affected significantly.
Conclusion. Our study demonstrates that CCL2 expression in sfd-FLSs is CAV1-dependent, but only at transcript level. As the function of CAV1 has not been unequivocally determined, more studies are needed to confirm the role of CAV1 in inflammatory processes related to RA.

Key words

rheumatoid arthritis, caveolin-1, C-C chemokine ligand 2/monocyte chemoattractant protein-1, synoviocytes

References (40)

  1. Bax M, van Heemst J, Huizinga TW, Toes RE. Genetics of rheumatoid arthritis: What have we learned? Immunogenetics. 2011;63(8):459–466.
  2. Bartok B, Firestein GS. Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233–255.
  3. Iwanaga T, Shikichi M, Kitamura H, Yanase H, Nozawa-Inoue K. Morphology and functional roles of synoviocytes in the joint. Arch Histol Cytol. 2000;63(1):17–31.
  4. Filer A. The fibroblast as a therapeutic target in rheumatoid arthritis. Curr Opin Pharmacol. 2013;13(3):413–419.
  5. Iwamoto T, Okamoto H, Toyama Y, Momohara S. Molecular aspects of rheumatoid arthritis: Chemokines in the joints of patients. FEBS J. 2008;275(18):4448–4455.
  6. Juarez M, Filer A, Buckley CD. Fibroblasts as therapeutic targets in rheumatoid arthritis and cancer. Swiss Med Wkly. 2012;142:w13529.
  7. Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: Passive responders and imprinted aggressors. Nat Rev Rheumatol. 2013;9(1):24–33.
  8. Harigai M, Hara M, Yoshimura T, Leonard EJ, Inoue K, Kashiwazaki S. Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium. Clin Immunol Immunopathol. 1993;69(1):83–91.
  9. Thurlings RM, Wijbrandts CA, Bennink RJ, et al. Monocyte scintigraphy in rheumatoid arthritis: The dynamics of monocyte migration in immune-mediated inflammatory disease. PLoS ONE. 2009;4(11): e7865.
  10. Jorgensen C, Apparailly F. Prospects for gene therapy in inflammatory arthritis. Best Pract Res Clin Rheumatol. 2010;24(4):541–552.
  11. Fujimoto T, Kogo H, Nomura R, Une T. Isoforms of caveolin-1 and caveolar structure. J Cell Sci. 2000;113(19):3509–3517.
  12. Anderson RG. The caveolae membrane system. Annu Rev Biochem. 1998;67:199–225.
  13. Torres VA, Tapia JC, Rodríguez DA, et al. Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin. J Cell Sci. 2006;119(9):1812–1823.
  14. Boscher C, Nabi IR. Caveolin-1: Role in cell signaling. Adv Exp Med Biol. 2012;729:29–50.
  15. Luanpitpong S, Talbott SJ, Rojanasakul Y, et al. Regulation of lung cancer cell migration and invasion by reactive oxygen species and caveolin-1. J Biol Chem. 2010;285(50):38832–38840.
  16. Head BP, Insel PA. Do caveolins regulate cells by actions outside of caveolae? Trends Cell Biol. 2006;17(2):51–57.
  17. Kimura A, Mora S, Shigematsu S, Pessin JE, Saltiel AR. The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1. J Biol Chem. 2002;277(33):30153–30158.
  18. Wang XM, Kim HP, Nakahira K, Ryter SW, Choi AM. The heme oxygenase-1/carbon monoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1. J Immunol. 2009;182(6): 3809–3818.
  19. Catalán V, Gómez-Ambrosi J, Rodríguez A, et al. Expression of caveolin-1 in human adipose tissue is upregulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation. Clin Endocrinol (Oxf). 2008;68(2):213–219.
  20. Zhang PX, Murray TS, Villella VR, et al. Reduced caveolin-1 promotes hyperinflammation due to abnormal heme oxygenase-1 localization in lipopolysaccharide-challenged macrophages with dysfunctional cystic fibrosis transmembrane conductance regulator. J Immunol. 2013;190(10):5196–5206.
  21. Takizawa N, Sawada S, Chosa N, Ishisaki A, Naruishi K. Secreted caveolin-1 enhances periodontal inflammation by targeting gingival fibroblasts. Biomed Res. 2013;34(1):1–11.
  22. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315–324.
  23. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–2581.
  24. Stebulis JA, Rossetti RG, Atez FJ, Zurier RB. Fibroblast-like synovial cells derived from synovial fluid. J Rheumatol. 2005;32(2):301–306.
  25. Scanu A, Oliviero F, Braghetto L, et al. Synoviocyte cultures from synovial fluid. Reumatismo. 2007;59(1):66–70.
  26. Baugé C, Girard N, Leclercq S, Galéra P, Boumédiene K. Regulatory mechanism of transforming growth factor beta receptor type II degradation by interleukin-1 in primary chondrocytes. Biochim Biophys Acta. 2012;1823(5):983–986.
  27. Hayer A, Stoeber M, Ritz D, Engel S, Meyer HH, Helenius A. Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation. J Cell Biol. 2010;191(3):615–629.
  28. Majkova Z, Smart E, Toborek M, Hennig B. Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent. Toxicol Appl Pharmacol. 2009;237(1):1–7.
  29. Li X, Gu X, Boyce TM, Zheng M, et al. Caveolin-1 increases proinflammatory chemoattractants and blood-retinal barrier breakdown but decreases leukocyte recruitment in inflammation. Invest Ophthalmol Vis Sci. 2014;55(10):6224–6234.
  30. Mirza MK, Yuan J, Gao XP, et al. Caveolin-1 deficiency dampens Toll-like receptor 4 signaling through eNOS activation. Am J Pathol. 2010; 176(5):2344–2351.
  31. Jiao H, Zhang Y, Yan Z, et al. Caveolin-1 Tyr14 phosphorylation induces interaction with TLR4 in endothelial cells and mediates MyD88-dependent signaling and sepsis-induced lung inflammation. J Immunol. 2013;191(12):6191–6199.
  32. Lv XJ, Li YY, Zhang YJ, Mao M, Qian GS. Over-expression of caveolin-1 aggravate LPS-induced inflammatory response in AT-1 cells via up-regulation of cPLA2/p38 MAPK. Inflamm Res. 2010;59(7):531–541.
  33. Yadav A, Saini V, Arora S. MCP-1: Chemoattractant with a role beyond immunity: A review. Clin Chim Acta. 2010;411(21–22):1570–1579.
  34. Ueda A, Okuda K, Ohno S, et al. NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. J Immunol. 1994;153(5):2052–2063.
  35. Garrean S, Gao XP, Brovkovych V, et al. Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to sepsis induced by lipopolysaccharide. J Immunol. 2006;177(7):4853–4860.
  36. Gardner CR, Gray JP, Joseph LB, et al. Potential role of caveolin-1 in acetaminophen-induced hepatotoxicity. Toxicol Appl Pharmacol. 2010;245(1):36–46.
  37. Li S, Seitz R, Lisanti MP. Phosphorylation of caveolin by src tyrosine kinases. The alpha-isoform of caveolin is selectively phosphorylated by v-Src in vivo. J Biol Chem. 1996;271(7):3863–3868.
  38. Kogo H, Aiba T, Fujimoto T. Cell type-specific occurrence of caveolin-1alpha and -1beta in the lung caused by expression of distinct mRNAs. J Biol Chem. 2004;279:25574–25578.
  39. Scherer PE, Tang Z, Chun M, Sargiacomo M, Lodish HF, Lisanti MP. Caveolin isoforms differ in their N-terminal protein sequence and subcellular distribution: Identification and epitope mapping of an isoform-specific monoclonal antibody probe. J Biol Chem. 1995; 270(27):16395–16401.
  40. Li S, Jin Z, Lu X. MicroRNA-192 suppresses cell proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes by downregulating caveolin 1. Mol Cell Biochem. 2017;432(1–2): 123–130.