| First Author | Gancz D | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 2 | Pages | 860-6 |
| PubMed ID | 22685314 | Mgi Jnum | J:189553 |
| Mgi Id | MGI:5446102 | Doi | 10.4049/jimmunol.1103451 |
| Citation | Gancz D, et al. (2012) A role for the NF-kappaB pathway in cell protection from complement-dependent cytotoxicity. J Immunol 189(2):860-6 |
| abstractText | Nucleated cells are equipped with several mechanisms that support their resistance to complement-dependent cytotoxicity (CDC). The role of the NF-kappaB pathway in cell protection from CDC was examined. Elevated sensitivity to CDC was demonstrated in cells lacking the p65 subunit of NF-kappaB or the IkappaB kinases IKKalpha or IKKbeta, and in cells treated with p65 small interfering RNA. Pretreatment with the IKK inhibitor PS-1145 also enhanced CDC of wild-type cells (WT) but not of p65(-/-) cells. Furthermore, reconstitution of p65 into p65(-/-) cells and overexpression of p65 in WT cells lowered their sensitivity to CDC. The postulated effect of p65 on the JNK-mediated death-signaling pathway activated by complement was examined. p65 small interfering RNA enhanced CDC in WT cells but not in cells lacking JNK. JNK phosphorylation induced by complement was more pronounced in p65(-/-) cells than in WT cells. The results indicate that the NF-kappaB pathway mediates cell resistance to CDC, possibly by suppressing JNK-dependent programmed necrotic cell death. |
