| First Author | Cataisson C | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 3 | Pages | 1686-92 |
| PubMed ID | 15661932 | Mgi Jnum | J:96402 |
| Mgi Id | MGI:3530399 | Doi | 10.4049/jimmunol.174.3.1686 |
| Citation | Cataisson C, et al. (2005) Protein kinase C alpha-mediated chemotaxis of neutrophils requires NF-kappa B activity but is independent of TNF alpha signaling in mouse skin in vivo. J Immunol 174(3):1686-92 |
| abstractText | Protein kinase C (PKC) isoforms are major regulators of cutaneous homeostasis and mediate inflammation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). We have previously reported that transgenic mice overexpressing PKCalpha in the skin exhibit severe intraepidermal neutrophilic inflammation and keratinocyte apoptosis when treated topically with TPA. Activation of PKCalpha increases the production of TNFalpha and the transcription of chemotactic factors (MIP-2, KC, S100A8/A9), vascular endothelial growth factor, and GM-CSF in K5-PKCalpha keratinocytes. In response to PKCalpha activation, NF-kappaB translocates to the nucleus and this is associated with IkappaB phosphorylation and degradation. Preventing IkappaB degradation reduces both the expression of inflammation-associated genes and chemoattractant release. To determine whether TNFalpha mediated NF-kappaB translocation and subsequent expression of proinflammatory factors, K5-PKCalpha mice were treated systemically with a dimeric soluble form of p75 TNFR (etanercept) or crossed with mice deficient for both TNFR isoforms, and keratinocytes were cultured in the presence of TNFalpha-neutralizing Abs. The in vivo treatment and TNFR deficiency did not prevent inflammation, and the in vitro treatment did not prevent NF-kappaB nuclear translocation after TPA. Together these results implicate PKCalpha as a regulator of a subset of cutaneous cytokines and chemokines responsible for intraepidermal inflammation independent of TNFalpha. PKCalpha inhibition may have therapeutic benefit in some human inflammatory skin disorders. |
