Hinweis zum Urheberrecht
Aufsatz zugänglich unter
URN: urn:nbn:de:bvb:29-opus-35743
URL: http://www.opus.ub.uni-erlangen.de/opus/volltexte/2012/3574/
Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation
Ellrichmann, Gisa ;
Thöne, Jan ;
Lee, De-Hyung ;
Rupec, Rudolph A. ;
Gold, Ralf ;
Linker, Ralf A.
| Originalveröffentlichung: |
| (2012) Journal of Neuroinflammation 9.15 (2012): 09.10.2012 <http://www.jneuroinflammation.com/content/9/1/15> |
| pdf-Format:
|
|
|
| SWD-Schlagwörter: |
| - |
| Freie Schlagwörter (Englisch): |
| NF-kappaB , myeloid cells , cytokines , experimental autoimmune encephalomyelitis |
| Collection: |
| Universität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / 2012 |
| Fakultät: |
| Medizinische Fakultät |
| DDC-Sachgruppe: |
| Medizin |
| Dokumentart: |
| Aufsatz |
| Sprache: |
| Englisch |
| Erstellungsjahr: |
| 2012 |
| Publikationsdatum: |
| 09.10.2012 |
| Kurzfassung in Englisch: |
|
The NF-κB/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-κB consists of a heterodimer which is complexed with its inhibitor, IκB. Conditional knockout-mice for IκBα in myeloid cells (lysMCreIκBαfl/fl) have been generated and are characterized by a constitutive activation of NF-κB proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS.
In comparison to controls, lysMCreIκBαfl/fl mice developed a more severe clinical course of EAE. Upon histological analysis on day 15 p.i., there was an over two fold increased infiltration of T-cells and macrophages/microglia. In addition, lysMCreIκBαfl/fl mice displayed an increased expression of the NF-κB dependent factor inducible nitric oxide synthase in inflamed lesions. These changes in the CNS are associated with increased numbers of CD11b positive splenocytes and a higher expression of Ly6c on monocytes in the periphery. Well in accordance with these changes in the myeloid cell compartment, there was an increased production of the monocyte cytokines interleukin(IL)-12 p70, IL-6 and IL-1beta in splenocytes. In contrast, production of the T-cell associated cytokines interferon gamma (IFN-gamma) and IL-17 was not influenced.
In summary, myeloid cell derived NF-κB plays a crucial role in autoimmune inflammation of the CNS and drives a pathogenic role of monocytes and macrophages independently from T-cells. |
Sie benötigen weitere Informationen?
Fragen Sie uns!