Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo.
Acne is the most common skin disease, causing significant psychosocial problems for those afflicted. Currently available agents for acne treatment, such as oral antibiotics and isotretinoin (Accutane), have limited use. Thus, development of novel agents to treat this disease is needed. However, the pathophysiology of acne inflammation is poorly understood. Before new therapeutic strategies can be devised, knowledge regarding molecular mechanisms of acne inflammation is required. We report here that transcription factors nuclear factor-kappaB and activator protein-1 are activated in acne lesions with consequent elevated expression of their target gene products, inflammatory cytokines and matrix-degrading metalloproteinases, respectively. These elevated gene products are molecular mediators of inflammation and collagen degradation in acne lesions in vivo. This new knowledge enables a rational strategy for development of pharmacological agents that can target the inflammation and matrix remodeling that occurs in severe acne.
Kang
Sewon
S
Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA. swkang@umich.edu
Cho
Soyun
S
Chung
Jin Ho
JH
Hammerberg
Craig
C
Fisher
Gary J
GJ
Voorhees
John J
JJ
D000152:Acne Vulgaris / Q000503:physiopathology*; D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016207:Cytokines; D016328:NF-kappa B; D011347:Procollagen; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D020782:Matrix Metalloproteinases