Importance of expression and polymorphisms of Toll-like receptors 2 and 4 in inflammatory diseases of the middle ear and its complications

Beograd : [A. D. Jotić]

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Medicina / Medicine

Uvod: Receptori slični toll-u (eng. Toll like receptors, TLR) imaju bitnu ulogu u aktivaciji početnog imunskog odgovora. Svaki opisani TLR prepoznaje određene mikrobiološke strukture ili molekulske obrasce patogena (eng. pathogen-associated molecular patterns, PAMP) i vezuje specifične ligande. Smatra se da je regulacija ekspresije TLR ima ulogu u patogenezi hroničnog otitisa, i da polimorfizmi u genima za TLR 2 i TLR4 mogu biti asocirani sa podložnošću akutnom otitisu i sekretornom hroničnom otitisu. Ova studija je imala za cilj da utvrdi postojanje ekspresije TLR2 i 4 na izmenjenoj sluznici srednjeg uva kod različitih formi hroničnih otitisa, kao i uticaj polimorfizma Arg753Gln u genu za TLR2 i polimorfizma Thr399Ile u genu za TLR4 i prisustvo bakterija na intenzitet početnog imunskog odgovora. Matrijal i metod istraživanja: Ova studija preseka je sprovedena na Klinici za otorinolaringologiju i maksilofacijalnu hirurgiju Kliničkog centra Srbije; Institutu za patologiju Medicinskog fakulteta Univerziteta u Beogradu i Laboratoriji za Radiobiologiju i molekularnu genetiku Instituta za nuklearne nauke Vinča u Beogradu, Univerziteta u Beogradu, u periodu od januara 2010.do decembra 2013 godine. Svi ispitanici su lečeni na Klinici za otorinolaringologiju i maksilofacijalnu hirurgiju Kliničkog Centra Srbije. Kontrolna grupa za ispitivanje ekspresije gena i proteina na sluznici srednjeg uva obuhvatila je 10 uzoraka makroskopski zdrave sluznice uzetih sa različitih delova srednjeg uva pacijenata lečenih od otoskleroze, kao nezapaljenskog procesa.. Kontrolna grupa za ispitivanje polimorfizama DNK obuhvatila je 100 uzoraka pune krvi pacijenata. Eksperimentalna grupa je obuhvatila uzorke tkiva i pune krvi 85 ispitanika; 45 (15 dece i 30 odraslih) operativno lečenih zbog hroničnog supurativnog otitisa bez holesteatoma; 30 (10 dece i 20 odraslih) zbog hroničnog otitisa sa holesteatomom; 10 bolesnika sa komplikacijama otitisa. Ekspresija proteina TLR 2 i TLR 4 se utvrđivala imunohistohemijskom metodom primenom specifičnih TLR 2 i TLR4 antitela...

Introduction: Toll-like receptors (TLRs) have a prominent role in inducing innate immune response. Each of described TLRs recognizes conserved microbial structures or pathogen-associated molecular patterns (PAMP) and has distinct ligands specifities. It has been suggested that regulation of TLRs is involved in the pathogenesis of chronic otitis media, and that TLR2 and TLR 4 polymorphisms were more or less successfully connected with susceptibility to acute otitis and chronic otitis with effusion. In this study, we wanted to establish expression of TLR 2 and 4 on middle ear mucosa in different types of chronic otitis media, and the influence of polymophisms TLR 2 rg753Gln and TLR 4 Thr399Ile and bacterial infection on the intensity of innate immune response. Material and methods: This study was conducted on Clinic for Otorhinolaryngology and Maxillofacial surgery, Clinical Centre of Serbia; Institute of Pathology of Medical Faculty in Belgrade and Laboratory for Radiobiology and Molecular Genetics of Vinca Institute of Nuclear Sciences, in the period from January 2010. to December 2013. All patients and control group subjects were treated on Clinic for otorhinolaryngology and maxillofacial surgery, Clinical Centre of Serbia in Belgrade. Control group for mucosal TLR expression consisted of 10 samles of middle ear mucosa taken from patients with otosclerosis. Control group for DNA polymophism detection consisted of 100 full blood samples in healthy subjects. Experimental group consisted of mucosal tissue samples and full blood samples of 85 patients; 45 treated of chronic otitis without cholesteatoma (15 children and 30 adults), 30 treated of chronic otitis with cholesteatoma (10 children and 20 adults) and 10 patients with complications of chronic otitis media with or without cholesteatoma. Expression of TLR 2 and 4 on middle ear mucosa was determined with immunohistochemical staining...

Hronični otitis, Toll-u sličan receptor (TLR) 2, TLR4, polimorfizmi

Chronic otitis media, Toll-like receptor (TLR) 2, TLR4, polymorphism

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