Benignus és malignus hiperproliferatív ill. gyulladásos bőrbetegségek pathomechanizmusának vizsgálata funkcionális genomikai módszerekkel = Studies on the pathomechanism of benign and malign hyperproliferative as well as inflammatory skin diseases by means of functional genomics

Pikkelysomorben vizsgaltuk a sejtciklus szabalyozasban reszt vevő extracellularis matrix protein, a fibronektin szerepet, es azonositottunk egy nem kodolo RNS gent (PRINS), mely szerepet jatszik a pikkelysomorre valo hajlam, ill. a sejtek stressz valaszanak kialakitasaban. A multifaktorialis etiologiaju labszarfekely genetikai hatterenek vizsgalata soran azonositottunk egy SNP-t, amely magasabb aranyban fordul elő a betegekben, mint egeszsegesekben, feltetelezzuk, hogy szerepet jatszik a betegseg pathogeneziseben. A serdulőkorban es gyakran meg a felnőttkorban is gondot jelentő acne vulgaris gyulladasos bőrbetegseg genomikai kutatasa soran igazoltuk, hogy az interleukin 1 receptor antagonista gen (IL-1RN) egy polimorfizmusa ebben a korkepben magasabb aranyban fordul elő, mint az egeszseges populacioban, amely pathogenetikai szerepere utal. Megmutattuk, hogy az acne pathomechanizmusaban kulcsfontossagu Propionibacterium acnes bakterium a keratinocitakban a veleszuletett immunitasban szerepet jatszo genek expressziojat indukalja. Vizsgaltuk a hisztamin szerepet az allergias kontakt dermatitisz pathogeneziseben. Kiserleteinkhez hisztidin dekarboxilaz knock-out egereket hasznaltunk, es eredmenyeink alapjan feltetelezzuk, hogy a hisztamin a kesői tipusu kontakt dermatitiszben negativ regulalo szerepet tolt be. A palyazat kereteben a gyulladasos bőrbetegsegek ill. a szenanatha kezelesere alkalmas uj fototerapias eljarasokat is fejlesztettunk es vizsgaltuk azok hatasmechanizmusat. | We investigated the role of an extracellular matrix protein, fibronectin (an important regulator of the cell cycle), in psoriasis. We identified a non-coding RNA gene, PRINS playing a role in cell stress, and a key factor of psoriasis susceptibility. The genetic background of the multifactorial leg ulcer was also studied. We discovered an SNP that is more frequent among leg ulcer patients than in controls. This finding suggests that this SNP might play a role in the pathogenesis of this disease. Acne vulgaris is another very common inflammatory skin disorder affecting a significant proportion of the teenager and the adult population. We showed that a polymorphism of the interleukin 1 receptor antagonist gene (IL1-RN) is more frequent among the affected individuals compared to healthy controls. This suggests a role for the IL1-RN gene in the development of this skin condition. Studies on the contribution of the skin colonizing Propionibacterium acne in the pathomechanism of acne showed that this bacterium induces the expression of genes playing a role in innate immunity of human kerationocytes. The role of histamine in allergic contact dermatitis was also investigated. We used histamine decarboxylase knock-out mice, and our results suggest that histamine plays a negative regulatory role in the late-type contact dermatitis. We have developed novel phototherapeutic methods for the treatment of inflammatory skin diseases and rhinitis allergica, and studied their mode of action.