Differential modulation of keratinocyte intercellular adhesion molecule-I expression by gamma interferon and phorbol ester: evidence for involvement of protein kinase C signal transduction.
There is growing evidence that keratinocyte (KC) intercellular adhesion molecule-I (ICAM-I) expression is involved in the epidermal trafficking of T lymphocytes. To further characterize the molecular basis of KC ICAM-I expression, the detailed kinetics of induction by gamma interferon (IFN-gamma), as well as the phorbol ester, 12-O tetradecanoylphorbol-13-acetate (TPA), were studied. This study reports that KCs express both the class II major histocompatibility antigen (HLA-DR) and ICAM-I in response to IFN-gamma, although the response is distinctive for each molecule. Also, TPA induces ICAM-I, but not HLA-DR expression, whilst the protein kinase inhibitor, H7, blocks the TPA, but not the IFN-gamma-mediated response. The results provide a molecular basis whereby non-cytokine-mediated stimuli (e.g. TPA) alter KC signal transduction events involving protein kinase-C (PK-C) and thereby generate such immunologically relevant events as ICAM-I expression. Thus, KCs may be targets for both T-cell derived cytokines (e.g. IFN-gamma), and non-cytokine TPA-like molecules which stimulate PK-C. Induction of ICAM-I by either mechanism would be capable of instigating intraepidermal T-cell trafficking.
Griffiths
C E
CE
Department of Dermatology, University of Michigan Medical Center, Ann Arbor 48109-0602.
Esmann
J
J
Fisher
G J
GJ
Voorhees
J J
JJ
Nickoloff
B J
BJ
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D015815:Cell Adhesion Molecules; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate