The role of nitric-oxide in CXCL12 expression regulation in experimental autoimmune encephalomyelitis in rats

Multipla skleroza (MS) je hronična, inflamatorna, demijelinizirajuća i degenerativna bolest centralnog nervnog sistema (CNS), koja se najčešće javlja kod mlañih osoba. Smatra se da imunski sistem ima ključnu ulogu u patogenezi MS, odnosno da bolest nastaje usled autoimunskog odgovora usmerenog prema proteinima mijelinskog omotača. MS je veoma raznolika bolest u svom kliničkom ispoljavanju, što je najverovatnije posledica različitih molekulskih mehanizama koji su uključeni u njenu patogenezu. Usled destrukcije mijelinskog omotača i degeneracije aksona neurona, dolazi do deficita u motornim, senzornim i kognitivnim funkcijama obolelih, koji mogu biti prolaznog ili trajnog karaktera. Trenutnim terapijskim pristupima može se uticati na odlaganje pojave novih neuroloških ispada i može se usporiti hronično pogoršavanje stanja kod pacijenata, ali se ne omogućava njihovo izlečenje. Eksperimentalni autoimunski encefalomijelitis (EAE) je najčešće korišćeni eksperimentalni model za proučavanje patofiziologije MS. Upotreba ovog modela, koji oponaša autoimunsku patogenezu MS, dovela je do mnogih saznanja o mehanizmima neuroimunoloških procesa, to jest, o prelasku imunskih ćelija iz krvotoka u CNS, o njihovoj interakciji sa lokalnim ćelijama glije i neuronima i o sledstvenoj inflamaciji, kao istaknutom aspektu MS. Hemokini su citokini koji imaju ključnu ulogu u regulaciji migracije imunskih ćelija na mesto inflamacije prilikom odbrane organizma od patogena ili tokom patoloških imunskih procesa, poput MS. Hemokini najčešće stimulišu imunski odgovor privlačenjem ćelija imunskog sistema na efektorska mesta, meñutim neki od njh ispoljavaju i regulatorne ili antiinflamatorne uloge, poput CXCL12. CXCL12 deluje antiinflamatorno sprečavanjem prelaska autoreaktivnih imunskih ćelija iz perivaskularnog prostora u parenhim CNS-a, izazivanjem apoptoze autoreaktivnih T ćelija i stimulisanjem promene proinflamatornog karaktera ovih ćelija u antiinflamatorni...Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS) that occurs preferentially in young adults. Immune system plays a key role in its pathogenesis. It is considered that MS develops due to an autoimmune response directed against myelin sheet components. MS is a very heterogeneous disease in its clinical manifestations, which is most probably a consequence of diverse molecular mechanisms involved in its pathogenesis. As a consequence of myelin sheet destruction and axonal degeneration, transient or permanent deficits in motor, sensory and cognitive functions appear in MS patients. Therapies which are currently in use decrease the frequency and the severity of acute attacks and slow down the rate of neurological deterioration, but do not cure the patients. Experimental autoimmune encephalomyelitis (EAE) is the most widely used experimental model for studying pathophysiology of MS. The use of this model, which mimics autoimmune pathogenesis of MS, led to many discoveries about neuroimmunological processes, such as egression of immune cells from the blood stream into the CNS, immune cell interaction with resident glial cells and neurons and subsequent inflammation, as an important aspect of MS. Chemokines are cytokines with a central role in regulation of immune cell migration at the site of inflammation during pathogen invasion and during pathological immune processes, such as MS. Most often, chemokines boost immune response by attracting immune cells at the effector sites. However, some chemokines, including CXCL12, exert regulatory or antiinflammatory roles. CXCL12 prevents egress of autoreactive immune cells from the perivascular space into the CNS parenchyma, induces autoreactive T cell apoptosis and stimulates shifting of proinflammatory phenotype of these cells towards antiinflammatory phenotype..