AKNE VULGARİSTE ENDOTELİN-1/NİTRİK OKSİT DENGESİ

Abstract

Amaç: Akne vulgaris’te plazma ET-1 ve NOx (nitrik oksidin metabolitleri olan nitrat/nitrit) konsantrasyon düzeylerini tayin etmek, ayrıca bu iki parametre ve hastalığın derecesi arasında bir ilişki olup olmadığını incelemek. Gereç ve yöntem: Akne vulgaris tanısı konmuş 30 hasta ile 20 sağlıklı kişinin plazma örneklerinde ET-1 ve NOx ölçümlendi. Bulgular: Akne vulgarisli hastalarda kontrol grubuna göre plazma ET-1 ve NOx düzeyleri anlamlı (p < 0,01) bir artış gösterdi. Kontrol grubunda ET-1 ve NOx arasında zayıf, fakat anlamlı bir negatif korelasyon (r= -0,456, p < 0,05) bulundu. Çalışma grubunda ise ET-1 ve NOx düzeyleri arasında bir korelasyon bulunmadı (r= -0,195, p= 0,302). Ayrıca, çalışma grubunda ET-1, NOx düzeyleri ve hastalık süresi arasında anlamlı korelasyonlar (r= 0,412, p < 0,05 ve r= 0,570, p < 0,01) olduğu gözlendi. Akne lezyonlarının derecesi ve ET-1, NOx düzeyleri arasında bir korelasyon bulunmadı. Sonuç:Akne vulgariste görülen plazma ET-1 ve NOx düzeylerindeki yükseliş muhtemelen artmış duktal hiperkornifikasyon, hiperkeratinizasyon ve sebum birikiminin sebebi ve/veya sonucu olabilir. Artmış olan ET-1 ve NOx üretimi keratinositlerde büyük olasılıkla büyüme, sitotoksik ve mitojenik factor gibi davranıyor olabilir. Çalışma grubunda ET-1 ve NOx arasında korelasyonun bulunmaması, akne lezyonlarının oluşmasına yol açan bu iki parametre arasındaki dengenin bozulduğunu yansıtmaktadır

Keywords

• Acne vulgaris, endotelin-1, nitrik oksit

References

1. Anggard E. Nitric oxide: mediator, murderer and medicine. Lancet 1994; 343: 1199-1206.
2. Basal E, Jain A, Kaushal GP. Antibody response to crude cell lysate of propionibacterium acnes and induction of pro-inf- lammatory cytokines in patients with acne and normal he- althy subjects. J Microbiol 2004; 42: 117-25.
3. Bialecka A, Mak M, Biedron R, Bobek M, Kasprowicz A, Marcinkiewicz J. Different pro-inflammatory and immuno- genic potentials of Propionibacterium acnes and Stapylococ- cus epidermidis: Implications for chronic inflammatory ac- ne. Arch Immunol Ther Exp 2005; 53: 79-85.
4. Bonifati C, Mussi A, Carducci M, Pittarello A, D’Auria L, Venuti A, Bagnato A, Salani D, Fazio M, Ameglio F. Endot- helin-1 levels are increased in sera and lesional skin extracts of psoriatic patients and correlate with disease severity. Ac- ta Derm Venereol (Stockh) 1998; 78: 22-26.
5. Bruch-Gerharz D, Ruzicka T, Kolb- Bachofen V. Nitric oxi- de and its implications in skin homeostasis and disease. Arch Dermatol Res 1998; 290: 643-651.
6. Bull HA, Hottershall J, Chowdhurry N, Cohen J, Dowd PM. Neuropeptides induce release of nitric oxide from human dermal microvascular endothelial cells. J Invest Dermatol 1996;106: 655-660.
7. Bull HA, Terenghi G, Bunker CB, Properzi G, Facer P, Po- lak JM, Dowd PM. Receptor binding by human cutaneus microvascular endothelium. J Invest Dermatol 1991;96: 999-103.
8. Gandhi CR, Berkowitz DE, Watkins D. Endothelins: Bioc- hemistry and pathophysiologic actions. Anestesiology 1994; 80: 892- 905.

9. Graham GM, Farrar MD, Cruse- Sawyer JE, Holland KT, Ingham E. Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. Acnes GroEL. Br J Dermatol 2004; 150: 421-428.
10. Grisham MB, Johnson GG, Lancaster JR. Quantitation of nitrate and nitrite in extracelluler fluids. Methods Enzymol 1996; 268: 237-246.
11. Ignarro, J.L. Signal transduction mechanisms involving nit- ric oxide. Biochem Pharmacol 1991; 15; 41: 485-90.
12. Imokawa G, Yada Y, Kimura M, Morisaki N. Granulocy- te/macrophage colony stimulating factor is an intrinsic kera- tinocyte-derived growth factor for human melanocytes in UVA- induced melanosis. Biochem J 1996; 313: 625-631.
13. Imokawa G, Yada Y, Kimura M. Signaling mechanism of en- dothelin- induced mitogenesis and melanogenesisin human melanocytes. Biochem J 1996; 314: 305-312.
14. Imokawa G, Yada Y, Miyagishi M. Endothelins secreted from human keratinocytes are intrinsic mitogens for human melanocytes. J Biol Chem 1992; 267: 24675-24680.
15. Jeremy AH, Holland DB, Roberts SG, Thomson KF, Cunlif- fe WJ: İnflammatory events are involved in acne lesion ini- tiation. J Invest Dermatol 2003; 121:20-27.
16. Holland DB, Jeremy AH: The role of inflammation in the pathogenesis of acne and acne scarring. Semin Cutan Med Surg 2005; 24: 79-83.
17. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Le- gaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL. Activation of toll-li- ke receptor 2 in Acne Triggers inflammatory cytokine res- ponses. J Immunol 2002; 169: 1535-1541.
18. Mills OH, Kligman AM. Ultraviolet phototheraphy and pho- tochemoteraphy of acne vulgaris. Arch Dermatol 1978; 114: 221-223.
19. Morhenn VB. Langerhans cells may trigger the psoriatic di- sease process via production of nitric oxide. Immunol Today 1997; 18: 433-436.
20. Notas G, Xidakis C, Valatas V, Kouroumalis A, Kourouma- lis E. Levels of circulating endothelin-1 and nitrates/nitrites in patients with virus-related hepatocellular carcinoma. J Vi- ral Hepatitis 2001; 8: 63-69.
21. Orem A, Aliyazicioglu R, Kiran E, Vanizor B, Cimnocodeit G, Deger O. The relationship between nitric oxide producti- on and activity of the disease in patients with psoriasis. Arch Dermatol 1997;133:1606-1607.
22. Qureshi AA, Lerner LH, Lerner EA. From bedside to the benchand back. Nitric oxide and the cutis. Arch Dermatol 1996; 132:889-893.
23. Schaller M, Loewenstein M, Borelli C, Jacob K, Vogeser M, Burgdorf WH, Plewig G. Induction of a chemoattractive pro- inflammatory cytokine response after stimulation of kerati- nocytes with Propionibacterium acnes and coproporphyrin III. Br J Dermatol 2005; 153: 66-71.
24. Sirsjö A, Karlsson M, Gidlöf A, Rollman O, Torma H. Inc- reased expression of inducible nitric oxide synthase in psori- atic skin and cytokine-stimulated cultured keratinocytes. Br J Dermatol 1996; 134: 643-648.
25. Suh DH, Kwon TE, Youn JI. Changes of comedonal cytoki- nes and sebum secretion after UV irradiation in acne pati- ents. Eur J Dermatol 2002; 12: 139-144.
26. Takuwa N, Takuwa Y, Yanagisawa M, Yamashita K, Masaki T. A novel vasoactive peptide endothelin stimulates mitoge- nesis through lipid turnover in Swiss 3T3 fibroblasts. J Biol Chem 1989; 264: 7856- 7861.
27. Tsuboi R, Sato C, Shi C. Endothelin-1 acts as an autocrine growht factor for normal keratinocytes. J Cell Physiol 1994; 159: 213-220.
28. Ural AU, Yalcin A, Beyan C, Isimer A, Bayhan H. Plasma Endothelin –1 concentrations in patients with Behçet’s dise- ase. Scand J Rheumatol 1994; 23: 322-325.
29. Vural P, Erzengin D, Canbaz M, Selcuki D. Nitric oxide and endothelin –1,2 in actinic keratosis and basal cell carcinoma: changes in nitric oxide/ endothelin ratio. Int J Dermatol 2001; 40: 704-708.
30. Wang R, Chahary A, Shen YJ, Scott PG, Tregdet EE. Human dermal fibroblasts produce nitric oxide synthase isoforms. J Invest Dermatol 1996; 106: 419-427.
31. Weller R. Nitric oxide- a newly discovered chemical trans- mitter in human skin. Br J Dermatol 1997; 137: 665-672.
32. Yada Y, Higuchi K, Imokawa G. Effects of endothelins in signal transduction and proliferation in human melanocytes. J Biol Chem 1991; 266:18352- 18357.
33. Zamora M, Morelli JG, Norris DA, Yohn JJ. Cultured human keratinocytes syntheise and secrete endothelin-1. J Invest Dermatol 1992; 98: 646-56.