Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-8-20
pubmed:abstractText
Skin keratinocytes are major mediators of host immune responses. The skin is also a target for immunologically based inflammation in many pathological states. Activation of protein kinase C (PKC) can induce cutaneous inflammation, but the precise role of each of six cutaneous PKC isoforms (alpha, delta, epsilon, eta, zeta, mu) that regulate normal skin homeostasis or contribute to skin pathology has not been clarified. We generated transgenic mice that overexpress PKCalpha in the basal layer of the epidermis and the outer root sheath of hair follicles under the regulation of the bovine keratin 5 promoter. K5-PKCalpha transgenic mice exhibit severe intraepidermal neutrophilic inflammation and disruption of the epidermis and upper hair follicles when treated topically with 12-O-tetradecanoylphorbol-13-acetate (TPA). Both TPA and UVB cause apoptosis in transgenic skin, but only TPA evokes intraepidermal inflammation. TPA also induces apoptosis in cultured transgenic keratinocytes, and this is prevented by an AP-1 dominant-negative construct. However, inhibiting AP-1 in vivo does not abrogate intraepidermal inflammation. Transcripts for specific cytokines and chemokines are elevated in TPA-treated cultured transgenic keratinocytes, and conditioned culture medium from these cells promotes neutrophil migration in vitro. Chemokine expression and neutrophil migration are not diminished by inhibiting AP-1. Thus, PKCalpha activation induces keratinocyte apoptosis via an AP-1-dependent pathway and mediates chemokine induction and intraepidermal inflammation independently. This model system will be useful to define specific chemokines regulated by PKCalpha that promote intraepidermal neutrophilic inflammation, a condition that characterizes several human cutaneous diseases such as pustular psoriasis and acute generalized exanthematous pustulosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2703-13
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12928424-Animals, pubmed-meshheading:12928424-Apoptosis, pubmed-meshheading:12928424-Cell Movement, pubmed-meshheading:12928424-Cell Survival, pubmed-meshheading:12928424-Cells, Cultured, pubmed-meshheading:12928424-Chemokines, pubmed-meshheading:12928424-Cytokines, pubmed-meshheading:12928424-Enzyme Activation, pubmed-meshheading:12928424-Epidermis, pubmed-meshheading:12928424-Inflammation, pubmed-meshheading:12928424-Keratinocytes, pubmed-meshheading:12928424-Mice, pubmed-meshheading:12928424-Mice, Inbred Strains, pubmed-meshheading:12928424-Mice, Transgenic, pubmed-meshheading:12928424-Protein Kinase C, pubmed-meshheading:12928424-Protein Kinase C-alpha, pubmed-meshheading:12928424-Signal Transduction, pubmed-meshheading:12928424-Transcription Factor AP-1, pubmed-meshheading:12928424-Transgenes
pubmed:year
2003
pubmed:articleTitle
Activation of cutaneous protein kinase C alpha induces keratinocyte apoptosis and intraepidermal inflammation by independent signaling pathways.
pubmed:affiliation
Laboratories of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article