Onur İSMİ, Kemal GÖRÜR, Yusuf VAYİSOĞLU, Tuba KARABACAK, Taylan GÜÇLÜTÜRK, Gürbüz POLAT, Cengiz ÖZCAN

Local Effect of Neurotrophin-3 in Neuronal Inflammation of Allergic Rhinitis: Preliminary Report

Background: Allergic rhinitis is a common inflamma-tory nasal mucosal disease characterized by sneezing, watery nasal discharge, nasal obstruction and itching. Although allergen-specific antibodies play a main role in the allergic airway inflammation, neuronal inflam-mation may also contribute to the symptoms of allergic rhinitis. Neuronal inflammation is primarily caused by the stimulation of sensory nerve endings with hista-mine. It has been shown that neurotrophins may also have a role in allergic reactions and neuronal inflam-mation. Nerve growth factor, neurotrophin 3 (NT-3), neurotrophin 4/5 and brain-derived neurotrophic fac-tor are members of the neurotrophin family. Although nerve growth factor and brain-derived neurotrophic factor are well studied in allergic rhinitis patients, the exact role of Neurotrophin-3 is not known.Aims: To investigate the possible roles of neurotroph-in-3 in allergic rhinitis patients.Study Design: Case-control study.Methods: Neurotrophin-3 levels were studied in the inferior turbinate and serum samples of 20 allergic rhi-nitis and 13 control patients. Neurotrophin-3 staining of nasal tissues was evaluated by immunohistochemis-try and ELISA was used for the determination of serum Neurotrophin-3 levels.Results: Neurotrophin-3 staining scores were statis-tically higher in the study group than in the control patients (p=0.001). Regarding serum Neurotrophin-3 levels, no statistically significant difference could be determined between allergic rhinitis and control pa-tients (p=0.156). When comparing the serum NT-3 levels with tissue staining scores, there were no sta-tistically significant differences in the allergic rhinitis and control groups (p=0.254 for allergic rhinitis and p=0.624 for control groups).Conclusion: We suggest that Neurotrophin-3 might af-fect the nasal mucosa locally without being released into the systemic circulation in allergic rhinitis patients

PDF

___

Wilson KF, Spector ME, Orlandi RR. Types of rhinitis. Otolar- yngol Clin N Am 2011;44:549-59.
Gelincik A, Aydin F, Ozerman B, Erguven M, Aydin S, Bilir A, et al. Enhanced nerve growth factor expression by mast cells does not differ significantly between idiopathic and allergic rhi- nitis. Ann Allergy Asthma Immunol 2012;108:396-401.
Sarin S, Undem B, Sanico A, Togias A. The role of the nervous system in rhinitis. J Allergy Clin Immunol 2006;118:999-1016.
Baraniuk JN, Druce HM. Neuroregulation of mucosal vascula- ture. In: Holgate ST, Busse WW, editors. Inflammatory mecha- nisms in asthma. Newyork: Marcel Dekker; 1998:619-37.
Kim D, Baraniuk JN. Neural aspects of allergic rhinitis. Curr Opin Otolaryngol Head Neck Surg 2007;15:268-73.
Takahashi Y, Kagawa Y, Izawa K, Ono R, Akagi M, Kamei C. Effect of histamine H4 receptor antagonist on allergic rhinitis in mice. Int Immunopharmacol 2009;9:734-8.
Nockher WA, Renz H. Neurotrophins and asthma: novel insight into neuroimmune interaction. J Allergy Clin Immunol 2006;117:67-71.
Rochlitzer S, Nassenstein C, Braun A. The contribution of neu- rotrophins to the pathogenesis of allergic asthma. Biochem Soc Trans 2006;34:594-9.
Quarcoo D, Fischer TC, Peckenschneider N, Groneberg DA, Welker P. High abundances of neurotrophin 3 in atopic dermati- tis mast cell. J Occup Med Toxicol 2009;4:8.
Abram M, Wegmann M, Fokuhl V, Sonar S, Luger EO, Kerzel S, et al. Nerve growth factor and neurotrophin-3 mediate survival of pulmonary plasma cells during the allergic airway inflamma- tion. J Immunol 2009;182:4705-12.
Renz H. The role of neurotrophins in bronchial asthma. Eur J Pharmacol 2001;429:231-7.
Bonini S, Lambiase A, Bonini S, Angelucci F, Magrini L, Manni L, et al. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma. Proc Natl Acad Sci U S A 1996;93:10955-60.
Raap U, Werfel T, Goltz C, Deneka N, Langer K, Bruder M, et al. Circulating levels of brain-derived neurotrophic factor cor- relate with disease severity in the intrinsic type of atopic derma- titis. Allergy 2006;61:1416-8.
O'Hanlon S, Facer P, Simpson KD, Sandhu G, Saleh HA, Anand P. Neuronal markers in allergic rhinitis: expression and correla- tion with sensory testing. Laryngoscope 2007;117:1519-27.
Barcena de Arellano ML, Wagner MF, Oldeweme J, Arnold J, Ebert A, Schneider A, et al. Neurotrophin expression is not affected in uteri of women with adenomyosis. J Mol Neurosci 2012;47:495-504.
Raap U, Fokkens W, Bruder M, Hoogsteden H, Kapp A, Braun- stahl GJ. Modulation of neurotrophin and neurotrophin receptor expression in nasal mucosa after nasal allergen provocation in allergic rhinitis. Allergy 2008;63:468-75.
Zhang SH, Rush RA. Neurotrophin 3 is increased in the sponta- neously hypertensive rats. J Hypertens 2001;19:2251-6.
Pata YS, Akbas Y, Unal M, Ozcan C, Gorur K, Talas DU. Dis- trubution of allergens among allergic rhinitis patients living in Mersin region. Kulak Burun Bogaz Ihtis Derg 2004;13:112-5.
Al Suleimani YM, Walker MJ. Allergic rhinitis and its pharma- cology. Pharmacol Ther 2007;114:233-60.
Dagnell C, Kemi C, Klominek J, Eriksson P, Sköld CM, Eklund A, et al. Effects of neurotrophins on human bronchial smooth muscle cell migration and matrix metalloproteinase-9 secretion. Transl Res 2007;150:303-10.
Noga O, Englmann C, Hanf G, Grützkau A, Seybold J, Kun- kel G. The production, storage and release of the neurotroph- ins nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 by human peripheral eosinophils in allergics and non-allergics. Clin Exp Allergy 2003;33:649-54.
Sanico AM, Stanisz AM, Gleeson TD, Bora S, Proud D, Bienen- stock J, et al. Nerve growth factor expression and release in al- lergic inflammatory disease of the upper airways. Am J Respir Crit Care Med 2000;161:1631-5.
Raap U, Deneka N, Bruder M, Kapp A, Wedi B. Differential up- regulation of neurotrophin receptors and functional activity of neurotrophins on peripheral blood eosinophils of patients with allergic rhinitis, atopic dermatitis and nonatopic subjects. Clin Exp Allergy 2008;38:1493-8.
Kobayashi H, Gleich GJ, Butterfield JH, Kita H. Human eosino- phils produce neurotrophins and secrete nerve growth factor on immunologic stimuli. Blood 2002;99:2214-20.
Noga O, Englmann C, Hanf G, Grützkau A, Guhl S, Kunkel G. Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences the function of eosinophils. Clin Exp Al- lergy 2002;32:1348-54.
Raap U, Braunstahl GJ. The role of neurotrophins in the patho- physiology of allergic rhinitis. Curr Opin Allergy Clin Immunol 2010;10:8-13.