Activation of toll-like receptors 2, 3 or 5 induces matrix metalloproteinase-1 and -9 expression with the involvement of MAPKs and NF-kappaB in human epidermal keratinocytes.
Toll-like receptors (TLRs) on epidermal keratinocytes are the first line of defense against microbe invasion, and matrix metalloproteases (MMPs) regulate inflammation, cell migration and wound healing. In this study, we demonstrate that the mRNA and protein expressions of MMP-1 and MMP-9 in human epidermal keratinocytes are induced by ligands for TLR2, TLR3 and TLR5 [Pam3CSK4, Poly(I:C) and flagellin, respectively] in a dose-dependent manner. We also found that the ligands for TLR2, TLR3 and TLR5 activate the MAP kinases, JNK and p38 MAPK, but not ERK1/2. Furthermore, treatment with the ligands for TLR2, TLR3 and TLR5 also induced the degradation of IkappaB-alpha and activated the nuclear translocation of NF-kappaB. MMP-1 induction by the ligands for TLR2, TLR3 and TLR5 was inhibited by pretreatment with BAY11-7082 (NF-kappaB inhibitor) or SP600125 (JNK inhibitor), whereas MMP-9 expression was inhibited by pretreatment with BAY11-7082, SP600125 or SB203580. These findings demonstrate that the activation of TLR2, TLR3 or TLR5 induces the expression of MMP-1 and MMP-9 in human epidermal keratinocytes. In addition, NF-kappaB or JNK mediated the MMP-1 expression induced by TLR2, TLR3 and TLR5, whereas NF-kappaB, JNK or p38 MAPK mediated the MMP-9 expression induced by TLR2, TLR3 and TLR5.
Lee
Youngae
Y
Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
Kim
Hyunjung
H
Kim
Sangmin
S
Kim
Kyu Han
KH
Chung
Jin Ho
JH
D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1