| First Author | Rebholz B | Year | 2008 |
| Journal | J Invest Dermatol | Volume | 128 |
| Issue | 7 | Pages | 1626-32 |
| PubMed ID | 18200059 | Mgi Jnum | J:137534 |
| Mgi Id | MGI:3801207 | Doi | 10.1038/sj.jid.5701234 |
| Citation | Rebholz B, et al. (2008) Role of NF-kappaB/RelA and MAPK pathways in keratinocytes in response to sulfur mustard. J Invest Dermatol 128(7):1626-32 |
| abstractText | Sulfur mustard (SM) is a strong vesicant that has been used as a chemical warfare agent. To understand the molecular mechanisms that underlie the inflammatory skin reaction in response to SM, we analyzed the activation pattern of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways. Keratinocytes responded with an induction of the canonical NF-kappaB pathway, including activation of IkappaB kinase 2, followed by phosphorylation and degradation of IkappaBalpha and of the transactivating subunit RelA at Ser536. The biphasic NF-kappaB response was strictly dependent on the transactivating subunit RelA, as demonstrated by keratinocytes lacking RelA. Parallel to NF-kappaB activation, we observed an induction of the Raf-1/MEK1/2/ERK1/2/MSK1 and MKK3/6/p38/MSK1 pathways. Although mitogen and stress-activated kinase 1 has been described as a RelA kinase with Ser276 as its target, this site remained unphosphorylated in response to SM. A further MAPK pathway induced by SM was the MKK4/7/JNK1/2 pathway, which resulted in phosphorylation of the transcription factor activating transcription factor-2, but not c-Jun. Our results indicate that SM induces a complex cellular response in keratinocytes, with the activation of three MAPK pathways and the NF-kappaB pathway. |
