Propionibacterium acnes stimulates pro-matrix metalloproteinase-2 expression through tumor necrosis factor-alpha in human dermal fibroblasts.
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.
Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.
Jee-Young
JY
Choi
Mei Shan
MS
Piao
Jee-Bum
JB
Lee
Jong Seok
JS
Oh
In-Gyu
IG
Kim
Seung-Chul
SC
Lee
D000152:Acne Vulgaris / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020405:Dermis / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D004318:Doxycycline / Q000494:pharmacology; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D004817:Epidermis / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D016908:Gram-Positive Bacterial Infections / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011425:Propionibacterium acnes / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004792:Enzyme Precursors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018093:Gelatinases; D008666:Metalloendopeptidases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline