Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation.

Anselm Sommer; Anja Fries; Isabell Cornelsen; Nancy Speck; Friedrich Koch Nolte; Gerald Gimpl; Jörg Andrä; Sucharit Bhakdi; Karina Reiss

Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation.

Standard

Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation. / Sommer, Anselm; Fries, Anja; Cornelsen, Isabell; Speck, Nancy; Koch Nolte, Friedrich; Gimpl, Gerald; Andrä, Jörg; Bhakdi, Sucharit; Reiss, Karina.

In: J BIOL CHEM, Vol. 287, No. 28, 28, 2012, p. 23678-23689.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sommer, A, Fries, A, Cornelsen, I, Speck, N, Koch Nolte, F, Gimpl, G, Andrä, J, Bhakdi, S & Reiss, K 2012, 'Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation.', J BIOL CHEM, vol. 287, no. 28, 28, pp. 23678-23689. <http://www.ncbi.nlm.nih.gov/pubmed/22613720?dopt=Citation>

APA

Sommer, A., Fries, A., Cornelsen, I., Speck, N., Koch Nolte, F., Gimpl, G., Andrä, J., Bhakdi, S., & Reiss, K. (2012). Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation. J BIOL CHEM, 287(28), 23678-23689. [28]. http://www.ncbi.nlm.nih.gov/pubmed/22613720?dopt=Citation

Vancouver

Sommer A, Fries A, Cornelsen I, Speck N, Koch Nolte F, Gimpl G et al. Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation. J BIOL CHEM. 2012;287(28):23678-23689. 28.

Bibtex

@article{86ac2db1bffd42e8a00e67eb25970105,

title = "Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation.",

abstract = "Melittin, the major component of the bee venom, is an amphipathic, cationic peptide with a wide spectrum of biological properties that is being considered as an anti-inflammatory and anti-cancer agent. It modulates multiple cellular functions but the underlying mechanisms are not clearly understood. Here, we report that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human HaCaT keratinocytes, melittin induced shedding of the adhesion molecule E-cadherin and release of TGF-?, which was accompanied by transactivation of the EGF receptor and ERK1/2 phosphorylation. This was followed by functional consequences such as increased keratinocyte proliferation and enhanced cell migration. Evidence is provided that ATP release and activation of purinergic P2 receptors are involved in melittin-induced ADAM activation. E-cadherin shedding and EGFR phosphorylation were dose-dependently reduced in the presence of ATPases or P2 receptor antagonists. The involvement of P2 receptors was underscored in experiments with HEK cells, which lack the P2X7 receptor and showed strikingly increased response to melittin stimulation after transfection with this receptor. Our study provides new insight into the mechanism of melittin function which should be of interest particularly in the context of its potential use as an anti-inflammatory or anti-cancer agent.",

keywords = "Animals, Humans, Cells, Cultured, Mice, Mice, Knockout, Models, Biological, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Western, Cell Line, Dose-Response Relationship, Drug, HEK293 Cells, Cadherins/metabolism, Receptor, Epidermal Growth Factor/metabolism, Extracellular Signal-Regulated MAP Kinases/metabolism, Cell Survival/drug effects, Adenosine Triphosphate/metabolism, Membrane Proteins/genetics/metabolism, Phosphorylation/drug effects, Receptors, Purinergic P2X7/genetics/*metabolism, ADAM Proteins/genetics/*metabolism, Amyloid Precursor Protein Secretases/genetics/metabolism, Embryo, Mammalian/cytology, Fibroblasts/cytology/drug effects/metabolism, Keratinocytes/cytology/*drug effects/metabolism, Melitten/*pharmacology, Animals, Humans, Cells, Cultured, Mice, Mice, Knockout, Models, Biological, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Western, Cell Line, Dose-Response Relationship, Drug, HEK293 Cells, Cadherins/metabolism, Receptor, Epidermal Growth Factor/metabolism, Extracellular Signal-Regulated MAP Kinases/metabolism, Cell Survival/drug effects, Adenosine Triphosphate/metabolism, Membrane Proteins/genetics/metabolism, Phosphorylation/drug effects, Receptors, Purinergic P2X7/genetics/*metabolism, ADAM Proteins/genetics/*metabolism, Amyloid Precursor Protein Secretases/genetics/metabolism, Embryo, Mammalian/cytology, Fibroblasts/cytology/drug effects/metabolism, Keratinocytes/cytology/*drug effects/metabolism, Melitten/*pharmacology",

author = "Anselm Sommer and Anja Fries and Isabell Cornelsen and Nancy Speck and {Koch Nolte}, Friedrich and Gerald Gimpl and J{\"o}rg Andr{\"a} and Sucharit Bhakdi and Karina Reiss",

year = "2012",

language = "English",

volume = "287",

pages = "23678--23689",

journal = "J BIOL CHEM",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

number = "28",

}

RIS

TY - JOUR

T1 - Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation.

AU - Sommer, Anselm

AU - Fries, Anja

AU - Cornelsen, Isabell

AU - Speck, Nancy

AU - Koch Nolte, Friedrich

AU - Gimpl, Gerald

AU - Andrä, Jörg

AU - Bhakdi, Sucharit

AU - Reiss, Karina

PY - 2012

Y1 - 2012

N2 - Melittin, the major component of the bee venom, is an amphipathic, cationic peptide with a wide spectrum of biological properties that is being considered as an anti-inflammatory and anti-cancer agent. It modulates multiple cellular functions but the underlying mechanisms are not clearly understood. Here, we report that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human HaCaT keratinocytes, melittin induced shedding of the adhesion molecule E-cadherin and release of TGF-?, which was accompanied by transactivation of the EGF receptor and ERK1/2 phosphorylation. This was followed by functional consequences such as increased keratinocyte proliferation and enhanced cell migration. Evidence is provided that ATP release and activation of purinergic P2 receptors are involved in melittin-induced ADAM activation. E-cadherin shedding and EGFR phosphorylation were dose-dependently reduced in the presence of ATPases or P2 receptor antagonists. The involvement of P2 receptors was underscored in experiments with HEK cells, which lack the P2X7 receptor and showed strikingly increased response to melittin stimulation after transfection with this receptor. Our study provides new insight into the mechanism of melittin function which should be of interest particularly in the context of its potential use as an anti-inflammatory or anti-cancer agent.

AB - Melittin, the major component of the bee venom, is an amphipathic, cationic peptide with a wide spectrum of biological properties that is being considered as an anti-inflammatory and anti-cancer agent. It modulates multiple cellular functions but the underlying mechanisms are not clearly understood. Here, we report that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human HaCaT keratinocytes, melittin induced shedding of the adhesion molecule E-cadherin and release of TGF-?, which was accompanied by transactivation of the EGF receptor and ERK1/2 phosphorylation. This was followed by functional consequences such as increased keratinocyte proliferation and enhanced cell migration. Evidence is provided that ATP release and activation of purinergic P2 receptors are involved in melittin-induced ADAM activation. E-cadherin shedding and EGFR phosphorylation were dose-dependently reduced in the presence of ATPases or P2 receptor antagonists. The involvement of P2 receptors was underscored in experiments with HEK cells, which lack the P2X7 receptor and showed strikingly increased response to melittin stimulation after transfection with this receptor. Our study provides new insight into the mechanism of melittin function which should be of interest particularly in the context of its potential use as an anti-inflammatory or anti-cancer agent.

KW - Animals

KW - Humans

KW - Cells, Cultured

KW - Mice

KW - Mice, Knockout

KW - Models, Biological

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Blotting, Western

KW - Cell Line

KW - Dose-Response Relationship, Drug

KW - HEK293 Cells

KW - Cadherins/metabolism

KW - Receptor, Epidermal Growth Factor/metabolism

KW - Extracellular Signal-Regulated MAP Kinases/metabolism

KW - Cell Survival/drug effects

KW - Adenosine Triphosphate/metabolism

KW - Membrane Proteins/genetics/metabolism

KW - Phosphorylation/drug effects

KW - Receptors, Purinergic P2X7/genetics/metabolism

KW - ADAM Proteins/genetics/metabolism

KW - Amyloid Precursor Protein Secretases/genetics/metabolism

KW - Embryo, Mammalian/cytology

KW - Fibroblasts/cytology/drug effects/metabolism

KW - Keratinocytes/cytology/drug effects/metabolism

KW - Melitten/pharmacology