Original Article

Subject Category: Connective Tissue

Journal of Investigative Dermatology (2008) 128, 846–854; doi:10.1038/sj.jid.5701188; published online 29 November 2007

Propionibacterium acnes Stimulates Pro-Matrix Metalloproteinase-2 Expression through Tumor Necrosis Factor-alpha in Human Dermal Fibroblasts

Jee-Young Choi1, Mei Shan Piao1, Jee-Bum Lee1, Jong Seok Oh2, In-Gyu Kim3 and Seung-Chul Lee1,4

  1. 1Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea
  2. 2Department of Microbiology, Chonnam National University Medical School, Gwangju, Korea
  3. 3Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul, Korea
  4. 4Clinical Trial Center, Chonnam National University Hospital, Gwangju, Korea

Correspondence: Dr Seung-Chul Lee, Department of Dermatology, Chonnam National University Medical School, 8 Hak-dong, Gwangju 501-757, Korea. E-mail: schul@chonnam.ac.kr

Received 13 June 2007; Revised 16 October 2007; Accepted 17 October 2007; Published online 29 November 2007.

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Abstract

Propionibacterium acnes (P. acnes) is a commensal microorganism found in sebum-rich skin and plays a role in acne inflammation by stimulating keratinocyte to produce a number of proinflammatory cytokines. However, the role of P. acnes in the dermis of acne lesions, where tissue remodeling after inflammation eventually takes place, is not known. In this study, we investigated whether P. acnes induces matrix metalloproteinase (MMP), a key enzyme involved in matrix remodeling in human dermal fibroblasts (hDF). We found that P. acnes increased expression of pro-matrix metalloproteinase (proMMP)-2 mRNA/protein in hDF, but not that of proMMP-9. Concomitantly, P. acnes induced tumor necrosis factor-alpha (TNF-alpha) mRNA/protein expression in hDF, which in turn increases both proMMP-2 mRNA and protein expression. P. acnes induced such changes through the activated NF-kappaB pathway. Doxycycline was found to inhibit the expression of proMMP-2 induced either by P. acnes or TNF-alpha. These results suggest that P. acnes stimulates hDF to produce TNF-alpha, which mediates the expression of proMMP-2 through the NF-kappaB pathway. The secretion of proMMP-2 from hDF upon P. acnes stimulation may contribute to the pathogenesis of tissue remodeling in acne skin.

Abbreviations:

hDF, human dermal fibroblast; MMP, matrix metalloproteinase; MT-MMP, membrane type MMP; P. acnes, Propionibacterium acnes; PBS, phosphate-buffered saline; proMMP, Pro-matrix metalloproteinase; TLR, Toll-like receptor; TNF-alpha, tumor necrosis factor-alpha

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