Heat shock-induced matrix metalloproteinase (MMP)-1 and MMP-3 are mediated through ERK and JNK activation and via an autocrine interleukin-6 loop.
Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of infrared radiation on skin aging. In addition to photons, heat is likely to be generated as a consequence of infrared irradiation, and heat shock is widely considered to be an environmental stress. Here we investigated the effect of heat shock on the expressions of matrix metalloproteinase (MMP)-1, MMP-2, and MMP-3 in cultured human skin fibroblasts. Heat shock induced the expression of MMP-1 and MMP-3, but not MMP-2, at the mRNA and protein levels in a temperature-dependent manner, and caused the rapid activation of three distinct mitogen-activated protein kinases (MAPK), extracelluar signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. The heat shock-induced MMP-1 and MMP-3 expression was suppressed by the inhibition of ERK and JNK but not by p38 MAPK inhibition. Furthermore, heat shock increased the synthesis and release of interleukin-6 (IL-6) into culture media. The specific inhibition of IL-6 using a monoclonal antibody against IL-6 greatly reduced the expression of MMP-1 and MMP-3 induced by heat shock. Taken together, our results suggest that ERK and JNK play an important role in the induction of MMP-1 and MMP-3 by heat shock and that the heat shock-induced expression of MMP-1 and MMP-3 is mediated via an IL-6-dependent autocrine mechanism.
Park
Chi-Hyun
CH
Department of Dermatology, Seoul National University College of Medicine and Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Lee
Min Jung
MJ
Ahn
Jungmi
J
Kim
Sangmin
S
Kim
Hyeon Ho
HH
Kim
Kyu Han
KH
Eun
Hee Chul
HC
Chung
Jin Ho
JH
D000906:Antibodies / Q000494:pharmacology; D019898:Autocrine Communication / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D020405:Dermis / Q000166:cytology / Q000201:enzymology*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D000906:Antibodies; D015850:Interleukin-6; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1