Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis and included in seronegative spondyloarthropathy. PsA has several unique characteristics different from rheumatoid arthritis (RA), such as enthesopathy, dactylitis, and abnormal bone remodeling. As compared with synovitis of RA (pannus), proliferation of PsA synovium is mild and characterized by hypervascularity and increased infiltration of polymorphonuclear leukocytes in the synovial tissues. Angiogenesis plays a crucial role in cutaneous psoriasis, and several angiogenic factors such as vascular endothelial growth factor, interleukin-8, angiopoietin, tumor necrosis factor-α and transforming growth factor-β, are suggested to play an important role also in the pathophysiology of PsA. Further, IL-17 has various functions such as upregulation of proinflammatory cytokines, attraction of neutrophils, stimulation of keratinocytes, endothelial cell migration, and osteoclast formation via RANKL from activated synovial fibroblasts. Thus, IL-17 may be important in angiogenesis, fibrogenesis, and osteoclastogenesis in PsA. In this paper, roles of angiogenesis in the psoriatic synovium are discussed, which may strengthen the understanding of the pathogenesis of PsA. 1. Introduction Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy in association with psoriasis. PsA is classified as one of the seronegative spondyloarthropathy characterized by joint destruction with extra-articular involvement (i.e., eye, gut, and bowel). The involved joints present swelling, redness, and deformity to the end, which are usually periphery (main involvements are distal interphalangeal joints), but sacroiliac joints are less frequently affected. In nearly 70% of patients, cutaneous lesions precede the onset of joint pain, in 20% arthropathy starts before skin manifestations, and in 10% both are contemporary. Results of laboratory examination show elevated levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) which reflect acute-phase inflammation. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies are usually negative. HLA-B27 is found chiefly in patients with spondylitis type PsA. Radiographic features of joint space narrowing, erosions, osteolysis, new bone formation, enthesitis, spur formation, pencil-in-cup appearance, and bamboo spine. Although, in general, patients with severe cutaneous psoriasis often complain of arthralgia, skin severity and joint lesions are not always parallel. A number of studies have suggested genetic,
References
[1]
D. L. Boyle and A. Kavanaugh, “The pathobiology of psoriatic synovium,” Current Opinion in Rheumatology, vol. 20, no. 4, pp. 404–407, 2008.
[2]
A. W. R. Van Kuijk and P. P. Tak, “Synovitis in psoriatic arthritis: immunohistochemistry, comparisons with rheumatoid arthritis, and effects of therapy,” Current Rheumatology Reports, vol. 13, no. 4, pp. 353–359, 2011.
[3]
T. Yamamoto, “Psoriatic arthritis: from a dermatological perspective,” European Journal of Dermatology, vol. 21, no. 5, pp. 660–666, 2011.
[4]
E. Kruithof, D. Baeten, L. De Rycke et al., “Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis,” Arthritis Research & Therapy, vol. 7, no. 3, pp. R569–R580, 2005.
[5]
R. A. Chua and J. L. Arbiser, “The role of angiogenesis in the pathogenesis of psoriasis,” Autoimmunity, vol. 42, no. 7, pp. 574–579, 2009.
[6]
R. Heidenreich, M. R？cken, and K. Ghoreschi, “Angiogenesis drives psoriasis pathogenesis,” International Journal of Experimental Pathology, vol. 90, no. 3, pp. 232–248, 2009.
[7]
M. Canavese, F. Altruda, T. Ruzicka, and J. Schauber, “Vascular endothelial growth factor (VEGF) in the pathogenesis of psoriasis—a possible target for novel therapies?” Journal of Dermatological Science, vol. 58, no. 3, pp. 171–176, 2010.
[8]
M. Ancelin, S. Chollet-Martin, M. A. Hervé, C. Legrand, J. El Benna, and M. Perrot-Applanat, “Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism,” Laboratory Investigation, vol. 84, no. 4, pp. 502–512, 2004.
[9]
C. Rosenberger, C. Solovan, A. D. Rosenberger et al., “Upregulation of hypoxia-inducible factors in normal and psoriatic skin,” Journal of Investigative Dermatology, vol. 127, no. 10, pp. 2445–2452, 2007.
[10]
M. Detmar, L. F. Brown, M. P. Sch？n et al., “Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice,” Journal of Investigative Dermatology, vol. 111, no. 1, pp. 1–6, 1998.
[11]
Y. Xia, B. Li, D. Hylton, M. Detmar, G. D. Yancopoulos, and J. S. Rudge, “Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis,” Blood, vol. 102, no. 1, pp. 161–168, 2003.
[12]
D. Voskas, N. Jones, P. Van Slyke et al., “A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice,” American Journal of Pathology, vol. 166, no. 3, pp. 843–855, 2005.
[13]
T. P. Singh, M. P. Sch？n, K. Wallbrecht, A. Gruber-Wackernagel, X.-J. Wang, and P. Wolf, “Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis,” PLOS ONE, vol. 8, no. 1, Article ID e51752, 2013.
[14]
J. R. Zibert, K. Wallbrecht, M. Sch？n et al., “Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions,” Journal of Clinical Investigation, vol. 121, no. 1, pp. 410–421, 2011.
[15]
R. Abe, S. Yamagishi, Y. Fujita et al., “Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis,” Journal of Dermatological Science, vol. 57, no. 3, pp. 183–191, 2010.
[16]
P. J. Costello, R. J. Winchester, S. A. Curran et al., “Psoriatic arthritis joint fluids are characterized by CD8 and CD4 T cell clonal expansions that appear antigen driven,” Journal of Immunology, vol. 166, no. 4, pp. 2878–2886, 2001.
[17]
T. Yamamoto, H. Yokozeki, and K. Nishioka, “Clinical analysis of 21 patients with psoriasis arthropathy,” Journal of Dermatology, vol. 32, no. 2, pp. 84–90, 2005.
[18]
L. Borgato, A. Puccetti, R. Beri et al., “The T cell receptor repertoire in psoriatic synovitis is restricted and T lymphocytes expressing the same TCR are present in joint and skin lesions,” Journal of Rheumatology, vol. 29, no. 9, pp. 1914–1919, 2002.
[19]
E. L. Ross, D. D'Cruz, and W. J. W. Morrow, “Localized monocyte chemotactic protein-1 production correlates with T cell infiltration of synovium in patients with psoriatic arthritis,” Journal of Rheumatology, vol. 27, no. 10, pp. 2432–2443, 2000.
[20]
J. D. Ca？ete, B. Santiago, T. Cantaert et al., “Ectopic lymphoid neogenesis in psoriatic arthritis,” Annals of the Rheumatic Diseases, vol. 66, no. 6, pp. 720–726, 2007.
[21]
H. A. Flytlie, M. Hvid, E. Lindgreen et al., “Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis,” Cytokine, vol. 49, no. 1, pp. 24–29, 2010.
[22]
G. Partsch, E. Wagner, B. F. Leeb, H. Br？ll, A. Dunky, and J. S. Smolen, “T cell derived cytokines in psoriatic arthritis synovial fluids,” Annals of the Rheumatic Diseases, vol. 57, no. 11, pp. 691–693, 1998.
[23]
A. W. R. Van Kuijk, P. Reinders-Blankert, T. J. M. Smeets, B. A. C. Dijkmans, and P. P. Tak, “Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment,” Annals of the Rheumatic Diseases, vol. 65, no. 12, pp. 1551–1557, 2006.
[24]
A. Di Cesare, P. Di Meglio, and F. O. Nestle, “The IL-23Th17 axis in the immunopathogenesis of psoriasis,” Journal of Investigative Dermatology, vol. 129, no. 6, pp. 1339–1350, 2009.
[25]
K. Wolk, H. S. Haugen, W. Xu et al., “IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not,” Journal of Molecular Medicine, vol. 87, no. 5, pp. 523–536, 2009.
[26]
Y. Zheng, D. M. Danilenko, P. Valdez et al., “Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis,” Nature, vol. 445, no. 7128, pp. 648–651, 2007.
[27]
J. R. Chan, W. Blumenschein, E. Murphy et al., “IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis,” Journal of Experimental Medicine, vol. 203, no. 12, pp. 2577–2587, 2006.
[28]
M. N. Hedrick, A. S. Lonsdorf, A. Shirakawa et al., “CCR6 is required for IL-23-induced psoriasis-like inflammation in mice,” Journal of Clinical Investigation, vol. 119, no. 8, pp. 2317–2329, 2009.
[29]
T. Kopp, P. Lenz, C. Bello-Fernandez, R. A. Kastelein, T. S. Kupper, and G. Stingl, “IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: evidence for enhanced cutaneous immunity,” Journal of Immunology, vol. 170, no. 11, pp. 5438–5444, 2003.
[30]
C. L. Danning, G. G. Illei, C. Hitchon, M. R. Greer, D. T. Boumpas, and I. B. McInnes, “Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis,” Arthritis & Rheumatism, vol. 43, no. 6, pp. 1244–1256, 2000.
[31]
D. Baeten, E. Kruithof, L. De Rycke et al., “Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy,” Arthritis Research & Therapy, vol. 7, no. 2, pp. R359–R369, 2005.
[32]
L. C. Zaba, I. Cardinale, P. Gilleaudeau et al., “Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses,” Journal of Experimental Medicine, vol. 204, no. 13, pp. 3183–3194, 2008.
[33]
S. L. Jongbloed, M. C. Lebre, A. R. Fraser et al., “Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis,” Arthritis Research & Therapy, vol. 8, no. 1, article R15, 2005.
[34]
F. Wang, E. Lee, M. A. Lowes et al., “Prominent production of IL-20 by CD68+/CD11c+ Myeloid-derived cells in psoriasis: gene regulation and cellular effects,” Journal of Investigative Dermatology, vol. 126, no. 7, pp. 1590–1599, 2006.
[35]
E. Guttman-Yassky, M. A. Lowes, J. Fuentes-Duculan et al., “Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis,” Journal of Immunology, vol. 181, no. 10, pp. 7420–7427, 2008.
[36]
R. Lande, E. Giacomini, B. Serafini et al., “Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tissue of patients with chronic inflammatory arthritis,” Journal of Immunology, vol. 173, no. 4, pp. 2815–2824, 2004.
[37]
F. O. Nestle and M. Gilliet, “Defining upstream elements of psoriasis pathogenesis: an emerging role for interferon α,” Journal of Investigative Dermatology, vol. 125, no. 5, pp. 14–15, 2005.
[38]
F. O. Nestle, C. Conrad, A. Tun-Kyi et al., “Plasmacytoid predendritic cells initiate psoriasis through interferon-α production,” Journal of Experimental Medicine, vol. 202, no. 1, pp. 135–143, 2005.
[39]
J. M. Curtsinger, J. O. Valenzuela, P. Agarwal, D. Lins, and M. F. Mescher, “Cutting edge: type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation,” Journal of Immunology, vol. 174, no. 8, pp. 4465–4469, 2005.
[40]
R. Koczulla, G. Von Degenfeld, C. Kupatt et al., “An angiogenic role for the human peptide antibiotic LL-37/hCAP-18,” Journal of Clinical Investigation, vol. 111, no. 11, pp. 1665–1672, 2003.
[41]
J. Wenzel, E. W？renk？mper, S. Freutel et al., “Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus,” Journal of Pathology, vol. 205, no. 4, pp. 435–442, 2005.
[42]
T. Yamamoto, M. Matsuuchi, K. Watanabe, I. Katayama, and K. Nishioka, “Mast cells in the synovium of patients with psoriasis arthropathy,” Dermatology, vol. 195, no. 1, pp. 73–74, 1997.
[43]
L. M. Klein, R. M. Lavker, W. L. Matis, and G. F. Murphy, “Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 22, pp. 8972–8976, 1989.
[44]
L. J. Walsh, G. Trinchieri, H. A. Waldorf, D. Whitaker, and G. F. Murphy, “Human dermal mast cells contain and release tumor necrosis factor α, which induces endothelial leukocyte adhesion molecule 1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 10, pp. 4220–4224, 1991.
[45]
R. J. Reece, J. D. Canete, W. J. Parsons, P. Emery, and D. J. Veale, “Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis,” Arthritis & Rheumatism, vol. 42, no. 7, pp. 1481–1484, 1999.
[46]
U. Fearon, K. Griosios, A. Fraser et al., “Angiopoietins, growth factors, and vascular morphology in early arthritis,” Journal of Rheumatology, vol. 30, no. 2, pp. 260–268, 2003.
[47]
D. J. Veale, C. Ritchlin, and O. FitzGerald, “Immunopathology of psoriasis and psoriatic arthritis,” Annals of the Rheumatic Diseases, vol. 64, no. 2, supplement, pp. ii26–ii29, 2005.
[48]
A. Mastroianni, E. Minutilli, A. Mussi et al., “Cytokine profiles during infliximab monotherapy in psoriatic arthritis,” British Journal of Dermatology, vol. 153, no. 3, pp. 531–536, 2005.
[49]
P. Cordiali-Fei, E. Trento, G. D'Agosto et al., “Effective therapy with anti-TNF-α in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions,” Annals of the New York Academy of Sciences, vol. 1110, pp. 578–589, 2007.
[50]
S. J. Leibovich, P. J. Polverini, H. M. Shepard, D. M. Wiseman, V. Shively, and N. Nuseir, “Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α,” Nature, vol. 329, no. 6140, pp. 630–632, 1987.
[51]
D. Veale, G. Yanni, S. Rogers, L. Barnes, B. Bresnihan, and O. FitzGerald, “Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis,” Arthritis & Rheumatism, vol. 36, no. 7, pp. 893–900, 1993.
[52]
U. Fiedler, Y. Reiss, M. Scharpfenecker et al., “Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation,” Nature Medicine, vol. 12, no. 2, pp. 235–239, 2006.
[53]
W. Gao, C. Sweeney, C. Walsh, et al., “Notch signaling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2,” Annals of Rheumatic Disease, vol. 72, no. 6, pp. 1080–1088, 2013.
[54]
M. Numasaki, J. Fukushi, M. Ono et al., “Interleukin-17 promotes angiogenesis and tumor growth,” Blood, vol. 101, no. 7, pp. 2620–2627, 2003.
[55]
M. S. Doyle, E. S. Collins, O. M. FitzGerald, and S. R. Pennington, “New insight into the functions of the interleukin-17 receptor adaptor protein Act1 in psoriatic arthritis,” Arthritis Research & Therapy, vol. 14, no. 5, article 226, 2012.
[56]
T. Noordenbos, N. Yeremenko, I. Gofita et al., “Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis,” Arthritis & Rheumatism, vol. 64, no. 1, pp. 99–109, 2012.
[57]
L. De Rycke, B. Vandooren, E. Kruithof, F. De Keyser, E. M. Veys, and D. Baeten, “Tumor necrosis factor α blockade treatment down-modulates the increased systemic and local expression of Toll-like receptor 2 and Toll-like receptor 4 in spondylarthropathy,” Arthritis & Rheumatism, vol. 52, no. 7, pp. 2146–2158, 2005.
[58]
R. Seibl, T. Birchler, S. Loeliger et al., “Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium,” American Journal of Pathology, vol. 162, no. 4, pp. 1221–1227, 2003.
[59]
Q. Zhang, W. Hui, G. J. Litherland et al., “Differential Toll-like receptor-dependent collagenase expression in chondrocytes,” Annals of the Rheumatic Diseases, vol. 67, no. 11, pp. 1633–1641, 2008.
[60]
F. Brentano, D. Kyburz, and S. Gay, “Toll-like receptors and rheumatoid arthritis,” Methods in Molecular Biology, vol. 517, pp. 329–343, 2009.
[61]
D. Kane, L. E. Jensen, S. Grehan, A. S. Whitehead, B. Bresnihan, and O. Fitzgerald, “Quantitation of metalloproteinase gene expression in rheumatoid and psoriatic arthritis synovial tissue distal and proximal to the cartilage-pannus junction,” Journal of Rheumatology, vol. 31, no. 7, pp. 1274–1280, 2004.
[62]
S. M. Sacre, E. Andreakos, S. Kiriakidis et al., “The toll-like receptor adaptor proteins MyD88 and Mal/TIRAP contribute to the inflammatory and destructive processes in a human model of rheumatoid arthritis,” American Journal of Pathology, vol. 170, no. 2, pp. 518–525, 2007.
[63]
S. Abdollahi-Roodsaz, L. A. B. Joosten, M. I. Koenders et al., “Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis,” Journal of Clinical Investigation, vol. 118, no. 1, pp. 205–216, 2008.
[64]
L. Candia, J. Marquez, C. Hernandez, A. H. Zea, and L. R. Espinoza, “Toll-like receptor-2 expression is upregulated in antigen-presenting cells from patients with psoriatic arthritis: a pathogenic role for innate immunity?” Journal of Rheumatology, vol. 34, no. 2, pp. 374–379, 2007.
[65]
B. Raffeiner, C. Dejaco, C. Duftner et al., “Between adaptive and innate immunity: TLR4-mediated perforin production by CD28null T-helper cells in ankylosing spondylitis,” Arthritis Research & Therapy, vol. 7, no. 6, pp. R1412–R1420, 2005.
[66]
B. Beutler, “Inferences, questions and possibilities in Toll-like receptor signalling,” Nature, vol. 430, no. 6996, pp. 257–263, 2004.
[67]
P. Costello, B. Bresnihan, C. O'Farrelly, and O. Fitzgerald, “Predominance of CD8+ T lymphocytes in psoriatic arthritis,” Journal of Rheumatology, vol. 26, no. 5, pp. 1117–1124, 1999.
[68]
I. Goldstein, A. J. Simon, S. B. Horin et al., “Synovial VLA-1+ T cells display an oligoclonal and partly distinct repertoire in rheumatoid and psoriatic arthritis,” Clinical Immunology, vol. 128, no. 1, pp. 75–84, 2008.
[69]
G. Partsch, G. Steiner, B. F. Leeb, A. Dunky, H. Br？ll, and J. S. Smolen, “Highly increased levels of tumor necrosis factor-α and other proinflammatory cytokines in psoriatric arthritis synovial fluid,” Journal of Rheumatology, vol. 24, no. 3, pp. 518–523, 1997.
[70]
G. Partsch, E. Wagner, B. F. Leeb, A. Dunky, G. Steiner, and J. S. Smolen, “Upregulation of cytokine receptors sTNF-R55, STNF-R75, and sIL-2r in psoriatic arthritis synovial fluid,” Journal of Rheumatology, vol. 25, no. 1, pp. 105–110, 1998.
[71]
A. Mitra, S. K. Raychaudhuri, and S. P. Raychaudhuri, “Functional role of IL-22 in psoriatic arthritis,” Arthritis Research & Therapy, vol. 14, article R65, 2012.
[72]
R. Sabat, S. Philipp, C. H？flich, et al., “Immunopathogenesis of psoriasis,” Experimental Dermatology, vol. 16, no. 10, pp. 779–798, 2007.
[73]
A. Spadaro, T. Rinaldi, V. Riccieri, G. Valesini, and E. Taccari, “Interleukin 13 in synovial fluid and serum of patients with psoriatic arthritis,” Annals of the Rheumatic Diseases, vol. 61, no. 2, pp. 174–176, 2002.
[74]
K. Wolk, E. Witte, E. Wallace et al., “IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis,” European Journal of Immunology, vol. 36, no. 5, pp. 1309–1323, 2006.
[75]
T. Loos, L. Dekeyzer, S. Struyf et al., “TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis,” Laboratory Investigation, vol. 86, no. 9, pp. 902–916, 2006.
[76]
A. Fraser, U. Fearon, R. Reece, P. Emery, and D. J. Veale, “Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis,” Arthritis & Rheumatism, vol. 44, no. 9, pp. 2024–2028, 2001.
