Keratinocyte Growth Inhibition by High-Dose Epidermal Growth Factor Is Mediated by Transforming Growth Factor β Autoinduction: A Negative Feedback Mechanism.

Slides:



Advertisements
Similar presentations
IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway  Hee Jung Kim, Seok Bean Song, Jung Min Choi, Kyung Moon Kim,
Advertisements

Volume 70, Issue 8, Pages (October 2006)
Antimicrobial Peptides Human β-Defensins Stimulate Epidermal Keratinocyte Migration, Proliferation and Production of Proinflammatory Cytokines and Chemokines 
Cdc42 Inhibits ERK-Mediated Collagenase-1 (MMP-1) Expression in Collagen-Activated Human Keratinocytes  Maryam G. Rohani, Brian K. Pilcher, Peter Chen,
Differential Regulation by IL-1β and EGF of Expression of Three Different Hyaluronan Synthases in Oral Mucosal Epithelial Cells and Fibroblasts and Dermal.
Myocardin-Related Transcription Factors A and B Are Key Regulators of TGF-β1- Induced Fibroblast to Myofibroblast Differentiation  Beverly J. Crider, George.
Birgit Stallmeyer, Heiko Kämpfer, Josef Pfeilschifter, Stefan Frank 
Linda Vi, Stellar Boo, Samar Sayedyahossein, Randeep K
Sphingosylphosphorylcholine is a Potent Inducer of Intercellular Adhesion Molecule-1 Expression in Human Keratinocytes  Genji Imokawa, Yutaka Takagi,
Topical Application of 17β-Estradiol Increases Extracellular Matrix Protein Synthesis by Stimulating TGF-β Signaling in Aged Human Skin In Vivo  Eui Dong.
Substance P Enhances the Production of Interferon-induced Protein of 10 kDa by Human Keratinocytes in Synergy with Interferon-γ  Naoko Kanda, Shinichi.
Epidermal Growth Factor Induces Fibronectin Expression in Human Dermal Fibroblasts via Protein Kinase C δ Signaling Pathway  Yoshihiro Mimura, Hironobu.
Insulin-Like Growth Factor-I Enhances Transforming Growth Factor-β-Induced Extracellular Matrix Protein Production Through the P38/Activating Transcription.
Keratinocyte Growth Regulation in Defined Organotypic Cultures Through IL-1-Induced Keratinocyte Growth Factor Expression in Resting Fibroblasts  Nicole.
IFN-γ Upregulates Expression of the Mouse Complement C1rA Gene in Keratinocytes via IFN-Regulatory Factor-1  Sung June Byun, Ik-Soo Jeon, Hyangkyu Lee,
Linda Vi, Stellar Boo, Samar Sayedyahossein, Randeep K
EGF Upregulates, Whereas TGF-β Downregulates, the Hyaluronan Synthases Has2 and Has3 in Organotypic Keratinocyte Cultures: Correlations with Epidermal.
IL-31 Receptor Alpha Expression in Epidermal Keratinocytes Is Modulated by Cell Differentiation and Interferon Gamma  Ruth Heise, Mark M. Neis, Yvonne.
Stefan W. Stoll, Jessica L. Johnson, Yong Li, Laure Rittié, James T
IGF-II-Mediated COX-2 Gene Expression in Human Keratinocytes Through Extracellular Signal-Regulated Kinase Pathway  Hye Jung Kim, Tae-Yoon Kim  Journal.
Decreased Growth Inhibitory Responses of Squamous Carcinoma Cells to Interferon-γ Involve Failure to Recruit cki Proteins into cdk2 Complexes  Beth L.
An Autocrine Loop Mediates Expression of Vascular Endothelial Growth Factor in Human Dermal Microvascular Endothelial Cells  Barbara Vega-Diaz, Serge.
Ketoconazole Suppresses Interleukin-4 plus Anti-CD40-Induced IgE Class Switching in Surface IgE Negative B Cells from Patients with Atopic Dermatitis 
Heparin-Binding Epidermal-Growth-Factor-Like Growth Factor Activation of Keratinocyte ErbB Receptors Mediates Epidermal Hyperplasia, a Prominent Side-Effect.
Cell-Density-Dependent Regulation of Expression and Glycosylation of Dopachrome Tautomerase/Tyrosinase-Related Protein-2  Thomas J. Hornyak, Daniel J.
Role of p38 MAPK in Transforming Growth Factor β Stimulation of Collagen Production by Scleroderma and Healthy Dermal Fibroblasts  Madoka Sato, Daniel.
Gangliosides GD1b, GT1b, and GQ1b Suppress the Growth of Human Melanoma by Inhibiting Interleukin-8 Production: the Inhibition of Adenylate Cyclase1 
Volume 132, Issue 5, Pages (May 2007)
Profiling Motility Signal-Specific Genes in Primary Human Keratinocytes  Chieh-Fang Cheng, Jianhua Fan, Balaji Bandyopahdhay, Dennis Mock, Shengxi Guan,
Olga M. Mazina, Marjorie A. Phillips, Trevor Williams, Carol A
Volume 53, Issue 6, Pages (June 1998)
Inhibitory Effect of β-Thujaplicin on Ultraviolet B-Induced Apoptosis in Mouse Keratinocytes  Takako Baba, Hajime Nakano, Katsuto Tamai, Daisuke Sawamura,
Histamine Inhibits the Production of Interferon-induced Protein of 10 kDa in Human Squamous Cell Carcinoma and Melanoma  Naoko Kanda, Shinichi Watanabe 
Naoko Kanda, Shinichi Watanabe  Journal of Investigative Dermatology 
Suppressor of Cytokine Signaling 1/JAB and Suppressor of Cytokine Signaling 3/Cytokine-Inducible SH2 Containing Protein 3 Negatively Regulate the Signal.
All-Trans-Retinoic Acid Induces Interleukin-8 via the Nuclear Factor-κB and p38 Mitogen-Activated Protein Kinase Pathways in Normal Human Keratinocytes 
Rosiglitazone Inhibits Proliferation, Motility, and Matrix Metalloproteinase Production in Keratinocytes  Narasimharao Bhagavathula, Kamalakar C. Nerusu,
Halofuginone, an Inhibitor of Type-I Collagen Synthesis and Skin Sclerosis, Blocks Transforming-Growth-Factor-β-Mediated Smad3 Activation in Fibroblasts 
17β-estradiol Inhibits the Production of RANTES in Human Keratinocytes
Differential Gene Induction of Human β-Defensins (hBD-1, -2, -3, and -4) in Keratinocytes Is Inhibited by Retinoic Acid  Jürgen Harder, Ulf Meyer-Hoffert,
The p38-MAPK/SAPK Pathway is Required for Human Keratinocyte Migration on Dermal Collagen  Wei Li, Celina Nadelman, Ginard Henry, Jianhua Fan, Matt Muellenhoff,
Dermatopontin Expression is Decreased in Hypertrophic Scar and Systemic Sclerosis Skin Fibroblasts and is Regulated by Transforming Growth Factor-β1,
Transforming Growth Factor β1 Induces Apoptosis in Normal Melanocytes but not in Nevus Cells Grown in Type I Collagen Gel  Tuomo Alanko  Journal of Investigative.
Hyaluronan Synthase 3 Regulates Hyaluronan Synthesis in Cultured Human Keratinocytes  Tetsuya Sayo, Yoshinori Sugiyama, Yoshito Takahashi, Naoko Ozawa,
IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway  Hee Jung Kim, Seok Bean Song, Jung Min Choi, Kyung Moon Kim,
Allergens and Irritants Transcriptionally Upregulate CD80 Gene Expression in Human Keratinocytes  Paul Wakem, Robert P. Burns, Francisco Ramirez, David.
Collagen Synthesis Is Suppressed in Dermal Fibroblasts by the Human Antimicrobial Peptide LL-37  Hyun Jeong Park, Dae Ho Cho, Hee Jung Kim, Jun Young.
Interferon-γ-Mediated Growth Regulation of Melanoma Cells: Involvement of STAT1- Dependent and STAT1-Independent Signals  Anja Bosserhoff  Journal of Investigative.
Deletion of the Homeobox Gene PRX-2 Affects Fetal but Not Adult Fibroblast Wound Healing Responses  Philip White, David W. Thomas, Steven Fong, Eric Stelnicki,
Smad3 and Extracellular Signal-Regulated Kinase 1/2 Coordinately Mediate Transforming Growth Factor-β-Induced Expression of Connective Tissue Growth Factor.
Interferon-γ, a Strong Suppressor of Cell Proliferation, Induces Upregulation of Keratin K6, One of the Inflammatory- and Proliferation-Associated Keratins 
Keratinocyte G2/M Growth Arrest by 1,25-Dihydroxyvitamin D3 Is Caused by Cdc2 Phosphorylation Through Wee1 and Myt1 Regulation  Xiuju Dai, Kenshi Yamasaki,
Post-Transcriptional Regulation of UV Induced TNF-α Expression
1α,25-Dihydroxyvitamin D3 Stimulates Activator Protein 1 DNA-Binding Activity by a Phosphatidylinositol 3-Kinase/Ras/MEK/Extracellular Signal Regulated.
Volume 70, Issue 5, Pages (September 2006)
Helium–Neon Laser Irradiation Stimulates Migration and Proliferation in Melanocytes and Induces Repigmentation in Segmental-Type Vitiligo  Hsin-Su Yu,
Keratinocytes Inhibit Expression of Connective Tissue Growth Factor in Fibroblasts In Vitro by an Interleukin-1α-Dependent Mechanism  Daniel Nowinski,
Blazej Zbytek, Andrzej T. Slominski 
STAT5a/PPARγ Pathway Regulates Involucrin Expression in Keratinocyte Differentiation  Xiuju Dai, Koji Sayama, Yuji Shirakata, Yasushi Hanakawa, Kenshi.
Naoko Kanda, Shinichi Watanabe  Journal of Investigative Dermatology 
Volume 70, Issue 8, Pages (October 2006)
John M. Lamar, Vandana Iyer, C. Michael DiPersio 
Naoko Kanda, Shinichi Watanabe  Journal of Investigative Dermatology 
Human Leukocyte Elastase Induces Keratinocyte Proliferation by Epidermal Growth Factor Receptor Activation  Ulf Meyer-Hoffert, Jana Wingertszahn, Oliver.
IL-12 Completely Blocks Ultraviolet-Induced Secretion of Tumor Necrosis Factor α from Cultured Skin Fibroblasts and Keratinocytes  Victoria P. Werth,
The Vitamin D Response Element of the Involucrin Gene Mediates its Regulation by 1,25-Dihydroxyvitamin D3  Daniel D. Bikle, Dean Ng, Yuko Oda, Karen Hanley,
Effects of Hepatocyte Growth Factor on the Expression of Type I Collagen and Matrix Metalloproteinase-1 in Normal and Scleroderma Dermal Fibroblasts 
Nerve Growth Factor Protects Human Keratinocytes from Ultraviolet-B-Induced Apoptosis  Alessandra Marconi, Cristina Vaschieri, Silvia Zanoli, Alberto.
Mechanism of Thymus- and Activation-Regulated Chemokine (TARC)/CCL17 Production and its Modulation by Roxithromycin  Mayumi Komine, Takashi Kakinuma,
Suppression of Keratinocyte Growth and Differentiation by Transforming Growth Factor β1 Involves Multiple Signaling Pathways  Alison L. Dahler, Lois L.
Presentation transcript:

Keratinocyte Growth Inhibition by High-Dose Epidermal Growth Factor Is Mediated by Transforming Growth Factor β Autoinduction: A Negative Feedback Mechanism for Keratinocyte Growth  Kenshi Yamasaki, Nobuko Toriu, Yasushi Hanakawa, Yuji Shirakata, Koji Sayama, Atsushi Takayanagi, Masafumi Ohtsubo, Shinobu Gamou, Nobuyoshi Shimizu, Makiko Fujii, Kohei Miyazono, Koji Hashimoto  Journal of Investigative Dermatology  Volume 120, Issue 6, Pages 1030-1037 (June 2003) DOI: 10.1046/j.1523-1747.2003.12239.x Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 STAT1 is involved in IFN-γ-dependent, but not in high doses of EGF-dependent, growth inhibition of human keratinocytes. Primary keratinocytes were seeded at 4.0×104 cells per well in six-well plates and cultured in MCDB153 medium with BHE. Twenty-four hours later, the medium was replaced with fresh MCDB153 without BHE. Adenovirus vectors (AxSTAT1F and AxCALacZ, m.o.i.=5) were added and the cells were incubated for 24 h. Then, the indicated concentrations of EGF (a) and IFN-γ (b) were added to the keratinocyte culture medium and the cells were incubated for 96 h. Cells were trypsinized, harvested, and counted, and the proliferation rates were calibrated by comparing the total numbers of stimulated and unstimulated cells. For the MTT assay, primary keratinocytes were seeded at 5.0×103 cells per well in 96-well plates. After transfection with adenovirus vectors, the indicated concentrations of EGF (c) and IFN-γ (d) were added. Ninety-six hours after stimulation, proliferation was determined by MTT assay. The values indicate proliferation relative to the respective unstimulated control. The bars and error bars represent mean and SD of three independent experiments. *p<0.05, **p<0.01, ***p<0.001. Journal of Investigative Dermatology 2003 120, 1030-1037DOI: (10.1046/j.1523-1747.2003.12239.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 EGF upregulates TGF-β mRNA. (a) EGF (10 ng per ml) was added to keratinocyte culture medium, and total RNA was extracted at 0, 1, 3, 6, 12, 24, 36, and 48 h after stimulation. Total RNA was hybridized with RNA probes, and separated on a polyacrylamide gel. Arrows on the left side of the panel indicate predicted TGF-β1, TGF-β2, and TGF-β3 mRNA bands. L32 and GAPDH are indicated as control mRNA. (b) Relative values of TGF-β1 and TGF-β2 mRNA were estimated using GAPDH as an internal reference, and normalized against the respective relative value at 0 h post-TGF-β2 stimulation. Journal of Investigative Dermatology 2003 120, 1030-1037DOI: (10.1046/j.1523-1747.2003.12239.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 EGF enhances the production of TGF-β. Keratinocytes were seeded at 5.0×105 per dish in 10 cm diameter collagen-coated dishes and cultured in 10 ml of MCDB153 medium with BHE. Forty-eight hours later, the medium was replaced with 10 ml fresh MCDB153 without BHE. Various concentrations of EGF (n=3) were added, and the cells were cultured for more than 3 d. Culture media were collected and the TGF-β1 and TGF-β2 concentration were measured by enzyme-linked immunosorbent assay. Error bars indicate ±SD. *p<0.05, **p<0.01. Journal of Investigative Dermatology 2003 120, 1030-1037DOI: (10.1046/j.1523-1747.2003.12239.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 EGF-dependent TGF-β signal activation. Keratinocytes were seeded at 4.0×104 per well in 12-well collagen-coated dishes and cultured in 1 ml of MCDB153 medium with BHE. Forty-eight hours later, the medium was replaced with 1 ml fresh MCDB153 without BHE, and AxdnALK5 or AxCALacZ were transfected (m.o.i.=5). Twenty-four hours after adenovirus transfection, 0.5 μg of p3TP-Lux (Wrana et al, 1992) and 10 ng of pRL-CMV were transfected. After a 10 h transfection of the reporter gene, media were replaced with 1 ml fresh MCDB153 without BHE. Various concentrations of EGF or 0.1 ng per ml of TGF-β1 were added to the medium and the cells were incubated for 72 h. Cells were harvested and luciferase activity was measured. Error bars indicate ±SD. Journal of Investigative Dermatology 2003 120, 1030-1037DOI: (10.1046/j.1523-1747.2003.12239.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 TGF-β and ALK5 are involved in EGF-dependent growth inhibition of keratinocytes. Keratinocytes were seeded at 4.0×104 cells per well in six-well collagen-coated dishes and cultured in 3 ml of MCDB153 medium with BHE. Twenty-four hours later, the medium was replaced with fresh MCDB153 without BHE. Adenovirus vectors (a) or anti-TGF-β1 monoclonal neutralizing antibody (1 ng per ml) (b) were added and the cells were incubated for 24 h for infection and gene expression. The indicated concentrations of EGF were added and the cells were incubated for 96 h. Cells were trypsinized, harvested, and counted, and the proliferation rates were calibrated by comparing the total numbers of stimulated and unstimulated cells. For the MTT assay, primary keratinocytes were seeded at 5.0×103 cells per well in 96-well plates. After transfection with adenovirus vectors (c), or addition of anti-TGF-β1 monoclonal neutralizing antibody (d), the indicated concentrations of EGF were added and the cells were cultured for 96 h. Proliferation was determined by MTT assay, and the values indicate proliferation relative to the respective unstimulated control. The bars and error bars represent the mean and SD of three independent experiments. *p<0.05, **p<0.01, ***p<0.001. Journal of Investigative Dermatology 2003 120, 1030-1037DOI: (10.1046/j.1523-1747.2003.12239.x) Copyright © 2003 The Society for Investigative Dermatology, Inc Terms and Conditions