All-trans retinoic acid shifts Propionibacterium acnes-induced matrix degradation expression profile toward matrix preservation in human monocytes.
The features of acne include excess sebum production, obstruction of the pilosebaceous duct caused by hyperkeratinisation, colonisation by Propionibacterium acnes and inflammation. The bacteria are thought to stimulate the production of inflammatory mediators (cytokines and chemokines) as a result of activation of the innate immune system. The present study investigates the action of P. acnes (as a 'sonicate') on human monocytes in culture in affecting the production and activities of the matrix metalloproteinases (MMPs), of which there are over 20 with different specificities that may be responsible for tissue destruction and, potentially, scarring. MMPs are produced as inactive precursors that require activation, but their enzymic activity seems to be more directly controlled by other proteins called TIMPs--tissue inhibitors of matrix metalloproteinases--which bind to them. In monocytes in culture, it was found that P. acnes sonicate (effectively broken, unfractionated cells) induced MMP-1 ('interstitial collagenase') and MMP-9 messenger RNAs, and the expression of MMP-9, but not of MMP-1 was dependent on Toll-like receptor-2. P. acnes sonicate also induced the expression of the mRNA for TIMP-1, the main regulator of MMP-1 and -9. Treatment of the monocytes with [10.sup.-7] M all-transretinoic acid decreased the expression of MMP-9, and combined treatment with both all-trans-retinoic acid and P. acnes sonicate inhibited the induction of both MMP-1 and MMP-9 while augmenting the expression of TIMP-1. This indicates that P. acnes induces the expression of the MMPs and that all-trans-retinoic acid treatment modulates the expression of both MMPs and TIMP-1. The effect of this would be to change the phenotype from a matrix-degrading to a matrix-preserving phenotype, explaining the therapeutic effects of all-trans-retinoic acid on acne.
In this paper a small amount of work on acne lesion biopsies is also presented. Inflamed acne lesions were taken by 4mm biopsy punch from three different patients and subjected to histological analysis using monoclonal antibodies to MMP-1 and MMP-3. Samples from all three patients showed staining for the two MMPs. No comparison with biopsied pilosebaceous units from non-acne is shown, although the authors state that others have demonstrated the presence of MMP-1 and -9 in acne lesions [1,2].
[1.] Papakonstantinou E, Aletras AJ, Glass E et al. Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Invest Dermatol, 2005, 125, 673-684.
2. Trivedi NR, Gililland KL, Zhoa W et al. Gene array expression profiling in acne lesions reveals marked up-regulation of genes involved in inflammation and matrix remodeling. J Invest Dermatol, 2006, 126, 1071-1079
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|Date:||Sep 1, 2008|
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