Popov Aleksandrov, A., Mirkov Ivana .,El-Muyghi, A. A. M., Glamodija Jasmin M Miljkovic Danijela Pokic J Ninkov Marina Kataranovski Dragan S & Kataranovski Milena V (2012) Differntial mechanisms of resistance to pulmonary Aspergillus fumigatus Infecti
Nitric oxide (NO) produced by inducible nitricoxide synthase (iNOS) within the central nervous system (CNS)mainly exerts adverse effects in neuroinflammation. Experimentalautoimmune encephalomyelitis (EAE), an animal model of multiplesclerosis, is a neuroinflammatory disorder. CXCL12 is a chemokine,whose antiinflammatory role in EAE has been described recently. Itsmajor producers in the CNS are astrocytes and endothelial cells ofmicro blood vessels (MBV). The aim of this work was to investigate invitro and in vivo effects of NO on CXCL12 gene expression in ratastrocytes and MBV.Materials and methods: Spinal cords (SC) were isolated from rats thatdeveloped EAE at different stages of the disease, homogenized andassessed for iNOS and CXCL12 gene expression by ‘real time’ RT-PCR.In vitro studies were performed on MBV isolated from SC of healthy,non-immunized adult rats, astrocytes derived from neonatal rats andC6 cells (rat astroglioma). After stimulation with supernatantscollected from splenocyte cultures stimulated with concanavalin Afor 48 h or with combination of cytokines (IL-1b + TNF + IFN-c + IL-17) they were exposed to NO donor, sodium-nitroprusside(SNP). Also, peritoneal cells isolated from healthy rats were co-cultivated with astrocytes. Nitrite accumulation in supernatants, asindirecte measure of NO release, was determined using Griess reactionand CXCL12 gene expression was measured by PCR. In vivo, ratsimmunized to develop EAE were treated with aminoguanidine, aninhibitor of iNOS activity, starting from day 9 post immunization,once per day until the disease peak was reached in control, untreatedgroup. At this point, CXCL12 gene expression was determined in SChomogenates and MBV.Results: We found negative correlation between gene expression ofiNOS and CXCL12 in SC of EAE rats. NO released from SNP orproduced by peritoneal cells in vitro significantly reduced CXCL12gene expression in astrocytes and MBV. In vivo inhibition of iNOS ledto upregulation of CXCL12 gene expression and reduction of EAEseverity in rats.Conclusions: These results imply that NO is important inhibitor ofCXCL12 expression within the CNS during the encephalitogenicautoimmune response. This adds to the list of harming effects of excessgeneration of NO in neuroinflammation
Amal Atia Mhfuod El- Muzghi, (9-2012)
