Expression of interferon-beta is associated with growth arrest of murine and human epidermal cells.
The cytokine interferon-beta is a regulator of cell replication and function, including invasion and induction of angiogenesis. The goal of this study was to determine whether the expression of interferon-beta by cells in the epidermis correlated with terminal differentiation. In situ hybridization analysis and immunohistochemical staining of formalin-fixed, paraffin-embedded specimens of normal human and murine epidermis and human and murine skin tumors of epithelial origin revealed that only differentiated, nondividing cells of the epidermis expressed interferon-beta protein. Keratinocyte cultures established from the epidermis of 3 d old mice were maintained under conditions permitting continuous cell division or induction of differentiation. Continuously dividing cells did not produce interferon-beta whereas nondividing differentiated cells expressing keratin 1 did. Growth-arrested, undifferentiated keratinocytes also expressed interferon-beta protein. Neutralizing interferon-beta in the culture medium inhibited differentiation, but the addition of exogenous interferon-beta did not stimulate differentiation. These data indicate that interferon-beta is produced by growth-arrested, terminally differentiated keratinocytes.
Bielenberg
D R
DR
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
McCarty
M F
MF
Bucana
C D
CD
Yuspa
S H
SH
Morgan
D
D
Arbeit
J M
JM
Ellis
L M
LM
Cleary
K R
KR
Fidler
I J
IJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D016899:Interferon-beta / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D053547:Keratin-14; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007633:Keratins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000906:Antibodies; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; D008565:Membrane Proteins; C064554:loricrin; D007633:Keratins; D016899:Interferon-beta; D002118:Calcium