Search

Abstract: Cholesterol is a major component of skin lipids and acts as a regulator of vesicular trafficking and signal transduction. However, the function of cholesterol on matrix metalloproteinases (MMPs) expression of human skin is not fully understood. Here, we investigated the effects of cholesterol on MMP-9 expression in normal human keratinocytes (NHK) and HaCaT cells. Basal level of MMP-9 expression was decreased by cholesterol in NHK. On the other hand, MMP-9 expression was increased by the cholesterol depletion agent, methyl-β-cyclodextrin (MβCD), while it was inhibited by cholesterol repletion in HaCaT cells. MβCD induced ERK and JNK phosphorylation were prevented by cholesterol repletion. The inhibition of ERK and JNK decreased MβCD-induced MMP-9 expression. Therefore, our results suggest that cholesterol regulates MMP-9 expression through ERK and JNK-dependent pathways. [Copyright &y& Elsevier]

Please cite this paper as: Activation of toll-like receptors 2, 3 or 5 induces matrix metalloproteinase-1 and -9 expression with the involvement of MAPKs and NF-κB in human epidermal keratinocytes. Experimental Dermatology 2010; 19: e44-e49. Abstract: 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 IκB-α and activated the nuclear translocation of NF-κB. MMP-1 induction by the ligands for TLR2, TLR3 and TLR5 was inhibited by pretreatment with BAY11-7082 (NF-κB 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-κB or JNK mediated the MMP-1 expression induced by TLR2, TLR3 and TLR5, whereas NF-κB, JNK or p38 MAPK mediated the MMP-9 expression induced by TLR2, TLR3 and TLR5. [ABSTRACT FROM AUTHOR]