REVIEW PAPER
The proinflammatory role of lipoxygenases in rheumatoid arthritis
| 1 | Department of Veterinary Hygiene, Voivodship Veterinary Inspectorate, Lublin, Poland |
| 2 | Department of Neonatology and Neonatal Intensive Care Unit, Independent Public Healthcare, Puławy, Poland |
CORRESPONDING AUTHOR
Jarosław Bryda
Department of Veterinary Hygiene, Voivodship Veterinary Inspectorate, Lublin, Poland, ul. Droga Męczenników Majdanka 50, 20-325 Lublin, Poland
Department of Veterinary Hygiene, Voivodship Veterinary Inspectorate, Lublin, Poland, ul. Droga Męczenników Majdanka 50, 20-325 Lublin, Poland
J Pre Clin Clin Res. 2018;12(4):129–134
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Rheumatoid arthritis (RA) is a chronic, systemic disease of connective tissue with autoimmune background. There is a lack of knowledge about the direct pathophysiological cause of RA formation. The involvement of lipoxygenase (LOX) in arachidonic acid (AA) metabolism can have a significant impact on the occurrence of RA. Significant role play a lipid mediators, inducing structural and metabolic changes in cells, that initiate the activation of proinflammatory pathways and immune responses.
Objective:
The purpose of this review is to analyze the involvement of LOX in the etiopathogenesis of RA, with particular emphasis on 5-LOX and 15-LOX, as well as characteristic of LOX enzymatic activity and identification of the role of AA metabolites in the inflammatory reaction process.
Description of the state of knowledge:
Effects of oxidative activity of LOX and dysfunctions of intracellular antioxidant systems lead to disturbance of redox homeostasis. The observed consequence of these phenomena are aberrations in the functioning of the immune system and the accompanying inflammation. In RA studies, increased activity of 5-LOX and its reaction products was observed, such as leukotrienes B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) in patients. A significant influence on the progression of RA is also associated with overexpression of 15-LOX, which leads to inhibition of chondrocyte proliferation and their apoptosis.
Conclusions:
The activity of the oxidative enzyme LOX is involved in the formation of lipid mediators responsible for inducing inflammation. The effects of the action of LOX there may be disorders of the immune system that contribute to the development of RA.
Rheumatoid arthritis (RA) is a chronic, systemic disease of connective tissue with autoimmune background. There is a lack of knowledge about the direct pathophysiological cause of RA formation. The involvement of lipoxygenase (LOX) in arachidonic acid (AA) metabolism can have a significant impact on the occurrence of RA. Significant role play a lipid mediators, inducing structural and metabolic changes in cells, that initiate the activation of proinflammatory pathways and immune responses.
Objective:
The purpose of this review is to analyze the involvement of LOX in the etiopathogenesis of RA, with particular emphasis on 5-LOX and 15-LOX, as well as characteristic of LOX enzymatic activity and identification of the role of AA metabolites in the inflammatory reaction process.
Description of the state of knowledge:
Effects of oxidative activity of LOX and dysfunctions of intracellular antioxidant systems lead to disturbance of redox homeostasis. The observed consequence of these phenomena are aberrations in the functioning of the immune system and the accompanying inflammation. In RA studies, increased activity of 5-LOX and its reaction products was observed, such as leukotrienes B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) in patients. A significant influence on the progression of RA is also associated with overexpression of 15-LOX, which leads to inhibition of chondrocyte proliferation and their apoptosis.
Conclusions:
The activity of the oxidative enzyme LOX is involved in the formation of lipid mediators responsible for inducing inflammation. The effects of the action of LOX there may be disorders of the immune system that contribute to the development of RA.
REFERENCES (64)
1.
Brash AR. Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem. 1999; 274(34): 23679–23682.
2.
Ivanov I, Heydeck D, Hofheinz K, Roffeis J, O’Donnell VB, Kühn H, et al. Molecular enzymology of lipoxygenases. Archives of biochemistry and biophysics. 2010; 503: 161–174.
3.
Porta H, Rocha-Sosa M. Plant lipoxygenases. Physiological and molecular features. Plant Physiol. 2002; 130(1): 15–21.
4.
Mashima R, Okuyama T. The role of lipoxygenases in pathophysiology; new insights and future perspectives. Redox Biol. 2015; 6: 297–310.
5.
Baraniak BM, Szymanowska U. Lipooksygenaza w żywności pochodzenia roślinnego [Lipoxygenase in food of plant origin]. ŻNTJ. 2006; 47(2): 29–45.
6.
Hayward S, Cilliers T, Swart. Lipoxygenases: From Isolation to Application. Compr Rev Food Sci Food Saf. 2016; 16(1): 199–211.
7.
Wecksler AT, Garcia NK, Holman TR. Substrate specificity effects of lipoxygenase products and inhibitors on soybean lipoxygenase-1. Bioorganic & medicinal chemistry. 2009; 17(18): 6534–6539.
8.
Dainese E, Sabatucci A, van Zadelhoff G, Angelucci CB, Vachette P, Veldink GA, et al. Structural stability of soybean lipoxygenase-1 in solution as probed by small angle X-ray scattering. J Mol Biol. 2005; 349(1): 143–152.
9.
Schilstra MJ, Veldink GA, Vliegenthart JF. The dioxygenation rate in lipoxygenase catalysis is determined by the amount of iron (III) lipoxygenase in solution. Biochemistry. 1994; 33(13): 3974–3979.
10.
Zheng Y, Brash AR. On the role of molecular oxygen in lipoxygenase activation: comparison and contrast of epidermal lipoxygenase-3 with soybean lipoxygenase-1. J Biol Chem. 2010; 285(51): 39876–39887.
11.
Seta A, Skórzyńska-Polit E, Szczuka E, Giełwanowska I. Lipooksygenaza w komórkach roślinnych – budowa i funkcja [Lipooxygenase in plant cells – structure and function]. Post Biol Kom. 2009; 36(25): 69–83.
12.
Kuhn H, Banthiya S, van Leyen K. Mammalian lipoxygenases and their biological relevance. Biochimica et biophysica acta. 2015; 1851(4): 308–330.
13.
Yang L, Ma C, Zhang L, Zhang M, Li F, Zhang C, et al. 15-Lipoxygenase-2/15(S)-hydroxyeicosatetraenoic acid regulates cell proliferation and metastasis via the STAT3 pathway in lung adenocarcinoma. Prostaglandins Other Lipid Mediat. 2018; 138: 31–40.
14.
Lauretti E, Praticò D. Novel Key Players in the Development of Tau Neuropathology: Focus on the 5-Lipoxygenase. J Alzheimers Dis. 2018; 64(s1): S481-S489.
15.
Afshinnia F, Zeng L, Byun J, Wernisch S, Deo R, Chen J, et al. Elevated lipoxygenase and cytochrome P450 products predict progression of chronic kidney disease. Nephrol Dial Transplant. 2018; doi: 10.1093/ndt/gfy232.
16.
Nowak JZ. Przeciwzapalne „prowygaszeniowe” pochodne wielonienasyconych kwasów tłuszczowych omega 3 i omega 6* [Anti-inflammatory pro-resolvingderivatives of omega-3 and omega-6 polyunsaturatedfatty acids]. Postepy Hig Med Dosw. 2010; 64: 115–132.
17.
Schneider I, Bucar F. Lipoxygenase Inhibitors from Natural Plant Sources. Part 2: Medicinal Plants with Inhibitory Activity on Arachidonate 12-lipoxygenase, 15-lipoxygenase and Leukotriene Receptor Antagonists. Phytother Res. 2005; 19(4): 263–272.
18.
Jelińska M. Kwasy tłuszczowe – czynniki modyfikujące procesy nowotworowe [Fatty acids – factors modifying cancer processes]. Biul Wydz Farm. AMW, 1, 2005.
19.
Wu R, Zhou W, Chen S, Shi Y, Su L, Zhu M, et al. Lipoxin A4 suppresses the development of endometriosis in an ALX receptor-dependent manner via the p38 MAPK pathway. Br J Pharmacol. 2014; 171(21): 4927–4940.
20.
Calabresi E, Petrelli F, Bonifacio AF, Puxeddu I, Alunno A. One year in review 2018: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2018; 36: 175–184.
22.
Ma VY, Chan L, Carruthers KJ. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil. 2014; 95(5): 986–995.
23.
Korczowska I. Rheumatoid arthritis susceptibility genes: An overview. World J Orthop. 2014; 5(4): 544–549.
24.
Batko B, Stajszczyk M, Świerkot J, Urbański K, Raciborski F, Jędrzejewski M, et al. Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide study. 2017.
25.
Tatara T, Snakowska P. Rola diety w reumatoidalnym zapaleniu stawów– przegląd systematyczny badań [The role of diet in rheumatoid arthritis – systematic review of research]. Med Rodz. 2015; 2(18): 70–78.
26.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3): 315–324.
27.
Saraux A, Berthelot JM, Chalès G, Le Henaff C, Thorel JB, Hoang S, et al. Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum. 2001; 44(11): 2485–2491.
28.
Gauhar U, Gaffo A, Alarcon G. Pulmonary Manifestations of Rheumatoid Arthritis. Semin Respir Crit Care Med. 2007; 28(4): 430–440.
29.
Young A, Koduri G. Extra-articular manifestations and complications of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2007; 21(5): 907–927.
30.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/ European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010; 69(9): 1580–1588.
31.
Picerno V, Ferro F, Adinolfi A, Valentini E, Tani C, Alunno A. One year in review: the pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2015; 33: 551–558.
32.
Mannik M, Nardella FA. IgG rheumatoid factors and self-association of these antibodies. Clin Rheum Dis. 1985; 11(3): 551–572.
33.
Van Boekel MA, Vossenaar ER, van den Hoogen FH, van Venrooij WJ. Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res. 2002; 4(2): 87–93.
34.
Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005; 4(3): 130–136.
35.
Matyska-Piekarska E, Łuszczewski A, Łącki J, Wawer I. Rola stresu oksydacyjnego w etiopatogenezie reumatoidalnego zapalenias tawów [The role of oxidative stress in the etiopathogenesis of rheumatoid arthritis] Postepy Hig Med Dosw. 2006; 60: 617–623.
36.
Orozco G, Barton A. Update on the genetic risk factors for rheumatoid arthritis. Expert Rev Clin Immunol. 2010; 6(1): 61–75.
37.
Kochi Y, Suzuki A, Yamamoto K. Genetic basis of rheumatoid arthritis: a current review. Biochem Biophys Res Commun. 2014; 452(2): 254–262.
38.
Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006; 11: 529–543.
39.
Welgus HG, Jeffrey JJ, Eisen AZ. The collagen substrate specificity of human skin fibroblast collagenase. J Biol Chem. 1981; 256(18): 9511–9515.
40.
Wojdasiewicz P, Poniatowski Ł.A, Szukiewicz D. The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis. Mediators of Inflammation. Mediators Inflamm. 2014; 2014:561459.
41.
Liagre B, Vergne-Salle P, Corbiere C, Charissoux JL, Beneytout JL. Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression. Arthritis Res Ther. 2004; 6(4): 373–383.
42.
Lee YH, Choi SJ, Kim A, Kim CH, Ji JD, Song GG. Expression of cyclooxygenase-1 and -2 in rheumatoid arthritis synovium. J Korean Med Sci. 2000; 15(1): 88–92.
43.
Kapoor M, Fumiaki K, Crofford LJ. Arachidonic acid-derived eicosanoids in rheumatoid arthritis: implications and future targets. Future Rheumatol. 2006; 1(3): 323–330.
44.
Lin HC, Lin TH, Wu MY, Chiu YC, Tang CH, Hour MJ, et al. 5-Lipoxygenase inhibitors attenuate TNF-alpha-induced inflammation in human synovial fibroblasts. PLoS One. 2014; 9(9):e107890.
45.
Bouchareychas L, Grössinger EM, Kang M, Qiu H, Adamopoulos IE. Critical Role of LTB4/BLT1 in IL-23-Induced Synovial Inflammation and Osteoclastogenesis via NF-κB. J Immunol. 2017; 198(1): 452–46.
46.
Di Gennaro A, Haeggström JZ. Targeting leukotriene B4 in inflammation. Expert Opin Ther Targets. 2014; 18(1): 79–93.
47.
Traianedes K, Dallas MR, Garrett IR, Mundy GR, Bonewald LF. 5-Lipoxygenase metabolites inhibit bone formation in vitro. Endocrinology. 1998; 139(7): 3178–84.
48.
Davidson EM, Rae SA, Smith MJ. Leukotriene B4, a mediator of inflammation present in synovial fluid in rheumatoid arthritis. Ann Rheum Dis. 1983; 42(6): 677–679.
49.
Gheorghe KR, Korotkova M, Catrina AI, Backman L, af Klint E, Claesson HE, et al. Expression of 5-lipoxygenase and 15-lipoxygenase in rheumatoid arthritis synovium and effects of intraarticular glucocorticoids. Arthritis Res Ther. 2009; 11(3):R83.
50.
Chen H, Dzitoyeva S, Manev H. 5-lipoxygenase in mouse cerebellar purkinje cells. Neuroscience. 2010; 171(2): 383–389.
51.
Ahmadzadeh N, Shingu M, Nobunaga M, Tawara T. Relationship between leukotriene B4 and immunological parameters in rheumatoid synovial fluids. Inflammation. 1991; 15: 497–503.
52.
Goetzl EJ, Pickett WC. The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs). J Immunol, 1980, 125(4) 1789–1791.
53.
Chabane N, Zayed N, Benderdour M, Martel-Pelletier J, Pelletier JP, Duval N. Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis. Arthritis Res Ther. 2009; 11(2):R44.
54.
Hulten LM, Olson FJ, Aberg H, Carlsson J, Karlstrom L, Boren J, et al. 15-Lipoxygenase-2 is expressed in macrophages in human carotid plaques and regulated by hypoxia-inducible factor-1alpha. Eur J Clin Investig. 2010; 40: 11–17.
55.
Magnusson LU, Lundqvist A, Karlsson MN, Skalen K, Levin M, Wiklund O, et al. Arachidonate 15-lipoxygenase type B knockdown leads to reduced lipid accumulation and inflammation in atherosclerosis. PLoS One. 2012; 7(8):e43142.
56.
Xu XC, Shappell SB, Liang Z, Song S, Menter D, Subbarayan V, et al. Reduced 15S-lipoxygenase-2 expression in esophageal cancer specimens and cells and upregulation in vitro by the cyclooxygenase-2 inhibitor, NS398. Neoplasia. 2003; 5: 121–127.
57.
Jiang WG, Watkins G, Douglas-Jones A, Mansel RE. Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer. Prostaglandins Leukot Essent Fatty Acids. 2006; 74: 235–245.
58.
Wang D, Chen S, Feng Y, Yang Q, Campbell BH, Tang X, et al. Reduced expression of 15-lipoxygenase 2 in human head and neck carcinomas. Tumour Biol. 2006; 27: 261–273.
59.
Kobe MJ, Neau DB, Mitchell CE, Bartlett SG, Newcomer ME. The structure of human 15-lipoxygenase-2 with a substrate mimic. J Biol Chem. 2014; 289(12): 8562–8569.
60.
Bazan NG, Musto AE, Knott EJ. Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity. Mol Neurobiol. 2011; 44: 216–222.
61.
Feltenmark S, Gautam N, Brunnstrom A, Griffiths W, Backman L, Edenius C, et al. Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells. Proc Natl Acad Sci USA. 2008; 105: 680–685.
62.
Liagre B, Vergne P, Rigaud M, Beneytout JL. Arachidonate 15-lipoxygenase of reticulocyte-type in human rheumatoid arthritis type B synoviocytes and modulation of its activity by proinflammatory cytokines. J Rheumatol. 1999; 26(5): 1044–1051.
63.
Chen K, Yan Y, Li C, Yuan J, Wang F, Huang P, et al. Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the pathogenesis of osteoarthritis. Cell Death Dis. 2017; 8(10):e3109.
64.
Yacoubian S, Serhan CN. New endogenous anti-inflammatory and proresolving lipid mediators: implications for rheumatic diseases. Nat Clin Pract Rheumatol. 2007, 3: 570–579.
RELATED ARTICLE
The Journal of Pre-Clinical and Clinical Research welcomes article
submissions and does not charge a publication fee.
Submit your article today and gain worldwide visibility for your article.
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.