An Autotaxin/Lysophosphatidic Acid/Interleukin-6 Amplification Loop Drives Scleroderma Fibrosis

Arthritis and Rheumatology

Volumn 68, Issue 12, 2016, Pages 2964-2974

  Castelino, Flavia V ^a   Bain, Gretchen ^b   Pace, Veronica A ^a   Black, Katharine E ^a   George, Leaya ^a   Probst, Clemens K ^a   Goulet, Lance ^b   Lafyatis, Robert ^c   Tager, Andrew M ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b PharmAkea Inc   (United States)

^c BOSTON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [6 CHLORO 7 FLUORO 2 METHYL 1 (1 PROPYL 1H PYRAZOL 4 YL 1H INDOL 3 YL SULFANYL)] 2 FLUOROBENZOIC SODIUM; AUTOTAXIN; BLEOMYCIN; ENZYME INHIBITOR; INTERLEUKIN 6; LYSOPHOSPHATIDIC ACID; UNCLASSIFIED DRUG; ALKYLGLYCEROPHOSPHOETHANOLAMINE PHOSPHODIESTERASE; BENZOIC ACID DERIVATIVE; IL6 PROTEIN, HUMAN; INTERLEUKIN-6, MOUSE; LYSOPHOSPHOLIPID; PAT-048; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; SMALL INTERFERING RNA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; FEMALE; GENE AMPLIFICATION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SCLERODERMA; SKIN FIBROBLAST; SKIN FIBROSIS; ANIMAL; CASE CONTROL STUDY; DISEASE MODEL; DRUG EFFECTS; ENZYME LINKED IMMUNOSORBENT ASSAY; FIBROBLAST; FIBROSIS; IMMUNOHISTOCHEMISTRY; METABOLISM; PATHOLOGY; REAL TIME POLYMERASE CHAIN REACTION; SKIN; SYSTEMIC SCLEROSIS;

ANIMALS; BENZOATES; BLEOMYCIN; CASE-CONTROL STUDIES; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; FIBROBLASTS; FIBROSIS; HUMANS; IMMUNOHISTOCHEMISTRY; INTERLEUKIN-6; LYSOPHOSPHOLIPIDS; MICE; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; REAL-TIME POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; SCLERODERMA, SYSTEMIC; SKIN;

EID: 84997683928     PISSN: 23265191     EISSN: 23265205     Source Type: Journal    
DOI: 10.1002/art.39797     Document Type: Article

References (43)

1. Castelino FV, Seiders J, Bain G, Brooks SF, King CD, Swaney JS, et al. Amelioration of dermal fibrosis by genetic deletion or pharmacologic antagonism of lysophosphatidic acid receptor 1 in a mouse model of scleroderma. Arthritis Rheum 2011;63:1405–15.
2. Mazereeuw-Hautier J, Gres S, Fanguin M, Cariven C, Fauvel J, Perret B, et al. Production of lysophosphatidic acid in blister fluid: involvement of a lysophospholipase D activity. J Invest Dermatol 2005;125:421–7.
3. Tokumura A, Carbone LD, Yoshioka Y, Morishige J, Kikuchi M, Postlethwaite A, et al. Elevated serum levels of arachidonoyl-lysophosphatidic acid and sphingosine 1-phosphate in systemic sclerosis. Int J Med Sci 2009;6:168–76.
4. Clements P, Lachenbruch P, Seibold J, White B, Weiner S, Martin R, et al. Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 1995;22:1281–5.
5. Steen VD, Medsger TA Jr. The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time. Arthritis Rheum 1997;40:1984–91.
6. Khanna D, Denton CP, Jagerschmidt A, Jasson M, Distler O, Allanore Y. SAR100842, an antagonist of lysophaphatidic acid receptor 1, as a potential treatment for patients with systemic sclerosis: results from a phase 2a study [abstract]. Arthritis Rheumatol 2014;66 Suppl:S387.
7. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, et al. LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol 2010;50:157–86.
8. Aoki J, Inoue A, Okudaira S. Two pathways for lysophosphatidic acid production. Biochim Biophys Acta 2008;1781:513–8.
9. Shimomura Y. Congenital hair loss disorders: rare, but not too rare. J Dermatol 2012;39:3–10.
10. Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M, et al. Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J Biol Chem 2006;281:25822–30.
11. Van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, et al. Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 2006;26:5015–22.
12. Watanabe N, Ikeda H, Nakamura K, Ohkawa R, Kume Y, Aoki J, et al. Both plasma lysophosphatidic acid and serum autotaxin levels are increased in chronic hepatitis C. J Clin Gastroenterol 2007;41:616–23.
13. Oikonomou N, Mouratis MA, Tzouvelekis A, Kaffe E, Valavanis C, Vilaras G, et al. Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol 2012;47:566–74.
14. Azare J, Doane A, Leslie K, Chang Q, Berishaj M, Nnoli J, et al. Stat3 mediates expression of autotaxin in breast cancer. PLoS One 2011;6:e27851.
15. Feghali CA, Bost KL, Boulware DW, Levy LS. Mechanisms of pathogenesis in scleroderma. I. Overproduction of interleukin 6 by fibroblasts cultured from affected skin sites of patients with scleroderma. J Rheumatol 1992;19:1207–11.
16. Hasegawa M, Fujimoto M, Matsushita T, Hamaguchi Y, Takehara K, Sato S. Serum chemokine and cytokine levels as indicators of disease activity in patients with systemic sclerosis. Clin Rheumatol 2011;30:231–7.
17. Khanna D, Denton C, van Laar JM, Jahreis A, Cheng S, Spotswood H, et al, for the FaSScinate Clinical Trial in Patients with SS. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis: week 24 data from a phase 2/3 trial [abstract]. Arthritis Rheumatol 2014;66 Suppl:S386.
18. Boucharaba A, Serre CM, Gres S, Saulnier-Blache JS, Bordet JC, Guglielmi J, et al. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest 2004;114:1714–25.
19. Van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737–47.
20. Nakamura K, Ohkawa R, Okubo S, Tozuka M, Okada M, Aoki S, et al. Measurement of lysophospholipase D/autotaxin activity in human serum samples. Clin Biochem 2007;40:274–7.
21. Tager AM, Lacamera P, Shea BS, Campanella GS, Selman M, Zhao Z, et al. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat Med 2008;14:45–54.
22. Tager AM, Kradin RL, LaCamera P, Bercury SD, Campanella GS, Leary CP, et al. Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10. Am J Respir Cell Mol Biol 2004;31:395–404.
23. Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 2002;158:227–33.
24. Amira Pharmaceuticals. Patent: autotaxin inhibitors and uses thereof. San Diego: World Intellectual Property Organization; 2012.
25. Sappino AP, Masouye I, Saurat JH, Gabbiani G. Smooth muscle differentiation in scleroderma fibroblastic cells. Am J Pathol 1990;137:585–91.
26. Kissin EY, Merkel PA, Lafyatis R. Myofibroblasts and hyalinized collagen as markers of skin disease in systemic sclerosis. Arthritis Rheum 2006;54:3655–60.
27. Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast: one function, multiple origins. Am J Pathol 2007;170:1807–16.
28. Khan K, Xu S, Nihtyanova S, Derrett-Smith E, Abraham D, Denton CP, et al. Clinical and pathological significance of interleukin 6 overexpression in systemic sclerosis. Ann Rheum Dis 2012;71:1235–42.
29. Desallais L, Avouac J, Frechet M, Elhai M, Ratsimandresy R, Montes M, et al. Targeting IL-6 by both passive or active immunization strategies prevents bleomycin-induced skin fibrosis. Arthritis Res Ther 2014;16:R157.
30. Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol 2003;73:713–21.
31. Kitaba S, Murota H, Terao M, Azukizawa H, Terabe F, Shima Y, et al. Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma. Am J Pathol 2012;180:165–76.
32. Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997;6:315–25.
33. Le TT, Karmouty-Quintana H, Melicoff E, Weng T, Chen NY, Pedroza M, et al. Blockade of IL-6 trans signaling attenuates pulmonary fibrosis. J Immunol 2014;193:3755–68.
34. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 1989;58:573–81.
35. Chalaris A, Garbers C, Rabe B, Rose-John S, Scheller J. The soluble interleukin 6 receptor: generation and role in inflammation and cancer. Eur J Cell Biol 2011;90:484–94.
36. Grisanti L, Rezza A, Clavel C, Sennett R, Rendl M. Enpp2/autotaxin in dermal papilla precursors is dispensable for hair follicle morphogenesis. J Invest Dermatol 2013;133:2332–9.
37. Pasternack SM, von Kugelgen I, Muller M, Oji V, Traupe H, Sprecher E, et al. In vitro analysis of LIPH mutations causing hypotrichosis simplex: evidence confirming the role of lipase H and lysophosphatidic acid in hair growth. J Invest Dermatol 2009;129:2772–6.
38. Rancoule C, Dusaulcy R, Treguer K, Gres S, Attane C, Saulnier-Blache JS. Involvement of autotaxin/lysophosphatidic acid signaling in obesity and impaired glucose homeostasis. Biochimie 2014;96:140–3.
39. Dusaulcy R, Rancoule C, Gres S, Wanecq E, Colom A, Guigne C, et al. Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid. J Lipid Res 2011;52:1247–55.
40. Marangoni RG, Korman B, Wei J, Wood TA, Graham L, Whitfield ML, et al. Myofibroblasts in cutaneous fibrosis originate from adiponectin-positive intradermal progenitors. Arthritis Rheumatol 2015;67:1062–73.
41. Milano A, Pendergrass SA, Sargent JL, George LK, McCalmont TH, Connolly MK, et al. Molecular subsets in the gene expression signatures of scleroderma skin. PLoS One 2008;3:e2696.
42. Sargent JL, Li Z, Aliprantis AO, Greenblatt M, Lemaire R, Wu MH, et al. Identification of optimal mouse models of systemic sclerosis by interspecies comparative genomics. Arthritis Rheumatol 2016;68:2003–15.
43. Wuyts WA, Antoniou KM, Borensztajn K, Costabel U, Cottin V, Crestani B, et al. Combination therapy: the future of management for idiopathic pulmonary fibrosis? Lancet Respir Med 2014;2:933–42.