Abstract
Activator protein-2 is an important transcription factor for the activation of a number of genes. Here we report the induction of activator protein-2 in response to inflammatory cytokines such as interleukin-6 in keratinocytes. Immunoblotting and semiquantitative reverse transcriptase- polymerase chain reaction assays using normal human keratinocytes revealed that interleukin-6 caused a time- and concentration-dependent induction of activator protein-2 mRNA and protein. The increase of activator protein-2 mRNA was detested at 30 min after stimulation and that of activator protein-2 protein was at 2 h. Their levels were lower than the control levels at 24 h. The interleukin-6-dependent induction of activator protein-2 mRNA was completely blocked by adding actinomycin D, whereas it was ≃ 50% affected by cycloheximide. Coincubation with neutralizing antibodies against various inflammatory cytokines resulted in inhibition of the interleukin-6-dependent activator protein-2 induction at varying degrees, indicating an involvement of various cytokines in the activator protein-2 induction. The activator protein-2 induction was observed in keratinocytes derived from lesional skins with psoriasis or squamous cell carcinoma, and the high levels of activator protein-2 were histochemically detected in these lesions. Furthermore, a gel mobility shift assay using the nuclear extracts from interleukin-6-treated cells showed that interleukin-6 induced the functional activator protein-2 protein for the gene activation. These findings suggest a possible regulation mechanism of activator protein-2 through a complex cytokine system, which is conceivably the initial reaction leading to skin inflammation, and resultant keratinocyte growth and carcinogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 600-606 |
| Number of pages | 7 |
| Journal | Journal of Investigative Dermatology |
| Volume | 113 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1999 |
| Externally published | Yes |
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Keywords
- Cell growth
- Psoriasis
- Squamous cell carcinoma
- Transcriptional activation
ASJC Scopus subject areas
- Dermatology
Cite this
Induction of transcription factor AP-2 by inflammatory cytokines in human keratinocytes. / Oyama, Noritaka; Iwatsuki, Keiji; Homma, Yoshimi; Kaneko, Fumio.
In: Journal of Investigative Dermatology, Vol. 113, No. 4, 1999, p. 600-606.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of transcription factor AP-2 by inflammatory cytokines in human keratinocytes
AU - Oyama, Noritaka
AU - Iwatsuki, Keiji
AU - Homma, Yoshimi
AU - Kaneko, Fumio
PY - 1999
Y1 - 1999
N2 - Activator protein-2 is an important transcription factor for the activation of a number of genes. Here we report the induction of activator protein-2 in response to inflammatory cytokines such as interleukin-6 in keratinocytes. Immunoblotting and semiquantitative reverse transcriptase- polymerase chain reaction assays using normal human keratinocytes revealed that interleukin-6 caused a time- and concentration-dependent induction of activator protein-2 mRNA and protein. The increase of activator protein-2 mRNA was detested at 30 min after stimulation and that of activator protein-2 protein was at 2 h. Their levels were lower than the control levels at 24 h. The interleukin-6-dependent induction of activator protein-2 mRNA was completely blocked by adding actinomycin D, whereas it was ≃ 50% affected by cycloheximide. Coincubation with neutralizing antibodies against various inflammatory cytokines resulted in inhibition of the interleukin-6-dependent activator protein-2 induction at varying degrees, indicating an involvement of various cytokines in the activator protein-2 induction. The activator protein-2 induction was observed in keratinocytes derived from lesional skins with psoriasis or squamous cell carcinoma, and the high levels of activator protein-2 were histochemically detected in these lesions. Furthermore, a gel mobility shift assay using the nuclear extracts from interleukin-6-treated cells showed that interleukin-6 induced the functional activator protein-2 protein for the gene activation. These findings suggest a possible regulation mechanism of activator protein-2 through a complex cytokine system, which is conceivably the initial reaction leading to skin inflammation, and resultant keratinocyte growth and carcinogenesis.
AB - Activator protein-2 is an important transcription factor for the activation of a number of genes. Here we report the induction of activator protein-2 in response to inflammatory cytokines such as interleukin-6 in keratinocytes. Immunoblotting and semiquantitative reverse transcriptase- polymerase chain reaction assays using normal human keratinocytes revealed that interleukin-6 caused a time- and concentration-dependent induction of activator protein-2 mRNA and protein. The increase of activator protein-2 mRNA was detested at 30 min after stimulation and that of activator protein-2 protein was at 2 h. Their levels were lower than the control levels at 24 h. The interleukin-6-dependent induction of activator protein-2 mRNA was completely blocked by adding actinomycin D, whereas it was ≃ 50% affected by cycloheximide. Coincubation with neutralizing antibodies against various inflammatory cytokines resulted in inhibition of the interleukin-6-dependent activator protein-2 induction at varying degrees, indicating an involvement of various cytokines in the activator protein-2 induction. The activator protein-2 induction was observed in keratinocytes derived from lesional skins with psoriasis or squamous cell carcinoma, and the high levels of activator protein-2 were histochemically detected in these lesions. Furthermore, a gel mobility shift assay using the nuclear extracts from interleukin-6-treated cells showed that interleukin-6 induced the functional activator protein-2 protein for the gene activation. These findings suggest a possible regulation mechanism of activator protein-2 through a complex cytokine system, which is conceivably the initial reaction leading to skin inflammation, and resultant keratinocyte growth and carcinogenesis.
KW - Cell growth
KW - Psoriasis
KW - Squamous cell carcinoma
KW - Transcriptional activation
UR - http://www.scopus.com/inward/record.url?scp=0032851350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032851350&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1747.1999.00734.x
DO - 10.1046/j.1523-1747.1999.00734.x
M3 - Article
C2 - 10504447
AN - SCOPUS:0032851350
VL - 113
SP - 600
EP - 606
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 4
ER -