Human keratinocytes acquire cellular cytotoxicity under UV-B irradiation. Implication of granzyme B and perforin.
Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin.
Hernandez-Pigeon
Hélène
H
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France. Electronic address: helene.hernandez@toulouse.inserm.fr.
Jean
Christine
C
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France.
Charruyer
Alexandra
A
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France.
Haure
Marie-José
MJ
CERPER, Institut de Recherche Pierre Fabre, Laboratoire de Biologie Cellulaire Cutanée, Toulouse, France.
Titeux
Matthias
M
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France.
Tonasso
Laure
L
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France.
Quillet-Mary
Anne
A
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France.
Baudouin
Caroline
C
CERPER, Institut de Recherche Pierre Fabre, Laboratoire de Biologie Cellulaire Cutanée, Toulouse, France.
Charveron
Marie
M
CERPER, Institut de Recherche Pierre Fabre, Laboratoire de Biologie Cellulaire Cutanée, Toulouse, France.
Laurent
Guy
G
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, Centre Hospitalier Universitaire Purpan, BP 3028, 31024 Toulouse cedex 3, France; Service d'Hématologie, Centre Hospitalier Universitaire Purpan, 31059 Toulouse, France.
D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000528:radiation effects; D053804:Granzymes; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008544:Melanocytes; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes; D014466:Ultraviolet Rays
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D066246:ErbB Receptors; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases