| First Author | Khaled AR | Year | 1997 |
| Journal | Clin Immunol Immunopathol | Volume | 83 |
| Issue | 3 | Pages | 254-63 |
| PubMed ID | 9175914 | Mgi Jnum | J:40472 |
| Mgi Id | MGI:87817 | Doi | 10.1006/clin.1997.4354 |
| Citation | Khaled AR, et al. (1997) Inhibition of the p50 (NKkappaB1) subunit of NF-kappaB by phosphorothioate-modified antisense oligodeoxynucleotides reduces NF-kappaB expression and immunoglobulin synthesis in murine B cells. Clin Immunol Immunopathol 83(3):254-63 |
| abstractText | NF-kappaB is a regulatory protein of immune response genes and a candidate for targeting in immunosuppressive therapy. NF-kappaB proteins are formed from components of which p50 (NFkappaB1) is a subunit. By targeting p50 gene expression with specific antisense 3' phosphorothioate-oligodeoxynucleotides (3' PS-ODNs), an effect upon NF-kappaB regulation and immunoglobulin synthesis in murine B cells was achieved. A 49% decrease in p50 protein was induced by treatment of WEHI 231 B cells with p50 antisense 3' PS-ODNs and not by control 3' PS-ODNs. p50 antisense specifically reduced the expression of NF-kappaB by 51%, but not the transcription factor, Oct-1. In the BXSB murine model of autoimmunity, p50 antisense inhibited NF-kappaB expression and total IgM and IgG synthesis, but, more importantly, dsDNA antibodies were reduced 90%. These results validate the use of p50 antisense to reduce NF-kappaB expression and, by downregulating the immune response, has application in the treatment of autoimmune disorders. |
