All-Trans Retinoic Acid Shifts Propionibacterium acnes-Induced Matrix Degradation Expression Profile toward Matrix Preservation in Human Monocytes

Abstract

Propionibacterium acnes is a critical component in the pathogenesis of acne vulgaris, stimulating the production of various inflammatory mediators, such as cytokines and chemokines, important in the local inflammatory response found in acne. This study explored the role of P. acnes and its ability to induce matrix metalloproteinases (MMPs) in primary human monocytes and how this induction is regulated by retinoids. MMP-1- and MMP-9-expressing cells were present in perifollicular and dermal inflammatory infiltrates within acne lesions, suggesting their role in acne pathogenesis. In vitro, we found that P. acnes induced MMP-9 and MMP-1 mRNA, and the expression of MMP-9, but not of MMP-1, was found to be Toll-like receptor 2-dependent. P. acnes induced the mRNA expression of tissue inhibitors of metalloproteinase (TIMP)-1, the main regulator of MMP-9 and MMP-1. Treatment of monocytes with all-trans retinoic acid (ATRA) significantly decreased baseline MMP-9 expression. Furthermore, co-treatment of monocytes with ATRA and P. acnes inhibited MMP-9 and MMP-1 induction, while augmenting TIMP-1 expression. These data indicate that P. acnes-induced MMPs and TIMPs may be involved in acne pathogenesis and that retinoic acid modulates MMP and TIMP expression, shifting from a matrix-degradative phenotype to a matrix-preserving phenotype.

Augmentation of Gene Expression and Production of Promatrix Metalloproteinase 2 by Propionibacterium acnes-Derived Factors in Hamster Sebocytes and Dermal Fibroblasts: A Possible Mechanism for Acne Scarring

“…We have also confirmed that gelatinolytic activity at approximately 92 kDa, which might correspond to proMMP-9, was negligible in sebocytes and dermal fibroblasts (data not shown). Since keratinocytes, monocytes, and dermal fibroblasts in hu-mans play important roles for MMP-mediated cutaneous ECM degradation in acne, 10,11,17,18) these results suggest that hamster sebocytes as well as dermal fibroblasts are useful for the investigation of sebaceous and pilosebaceous ECM remodeling in acne lesion.…”

“…[13][14][15] We recently reported that P. acnes directly augments sebum production in hamster sebaceous glands in vivo and in vitro. 16) In addition, P. acnes has also been reported to augment the expression of proMMPs-1 and -9 in human monocytes 17) and that of proMMP-2 in human dermal fibroblasts. 18) However, it remains unclear whether or not P. acnes directly regulates MMP production in sebaceous glands that may be associated with the onset of scar formation in acne.…”

Provitamin A carotenoids are independently associated with matrix metalloproteinase-9 in plasma samples from a general population

“…Carotenoids, in particular β-carotene, have been shown to inhibit the synthesis and activation of MMP-9 in cell lines and mouse models [30][31][32]. Emerging evidence indicates that retinoids, the metabolically active derivatives of vitamin A, exhibit effects on vascular cells and have anti-inflammatory properties that may be [40][41][42].…”

Inhaled all-trans retinoic acid in an individual with severe emphysema: Table 1—

“…RA has been demonstrated to promote alveolarisation in a rat model [1], but other reports in rats and mice failed to demonstrate such an effect [2][3][4][5]. Furthermore, ATRA can improve the protease/anti-protease balance [6,7] and has anti-inflammatory activity [8]. Oral therapy with ATRA in chronic obstructive pulmonary disease (COPD) has been reported and there is evidence of some improvement [9,10].…”