Recombinant erythropoietin down-regulates IL-6 and CXCR4 genes in TNF-alpha-treated primary cultures of human microvascular endothelial cells: implications for multiple sclerosis.
In multiple sclerosis (MS), disruption of the blood-brain barrier might lead to new gadolinium-enhanced lesion formation in the brain and cause acute relapses. Current therapeutic options for acute relapses in MS are limited. The effect of recombinant erythropoietin (rEPO) on cytokine gene expression in TNF-alpha-treated human brain microvascular endothelial cells was studied. The cells were controls (untreated), exposed for either 6 or 24 h to TNF-alpha or TNF-alpha/rEPO. Of the 96 genes studied, interleukin-6 (IL-6), IL-1beta, CXCR4, and IL-1alpha genes were down-regulated when treated with TNF-alpha/rEPO for 6 h as compared with TNF-alpha alone. At 24 h, IL-6 and CXCR4 gene expression was 4.24 and 2.98, respectively. Quantitative RT-PCR analysis showed down-regulation by 3.86 and 1.9 for IL-6 and CXCR4 genes, respectively. Our findings suggest that further studies are warranted to evaluate the use of EPO in minimizing acute relapses in MS.
Avasarala
Jagannadha R
JR
Departments of Neurology and Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. jagan@wfubmc.edu
Konduru
Sastry S
SS
D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D019718:Receptors, CXCR4 / Q000235:genetics*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015850:Interleukin-6; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin