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

Abstract

Aberrant extracellular matrix (ECM) remodeling in sebaceous glands and pilosebaceous units in the skin is associated with scar formation under acne conditions. To investigate the involvement of Propionibacterium acnes (P. acnes), a Gram-positive anaerobic microbial species, in ECM remodeling in sebaceous glands and pilosebaceous units, we examined the effects of P. acnes culture media, formalin-fixed P. acnes, and peptidoglycan (PGN) from Gram-positive bacteria walls on the production of promatrix metalloproteinase 2 (proMMP-2)/progelatinase A in hamster sebocytes and dermal fibroblasts. When hamster sebocytes (1.8؋10 5 cells) and dermal fibroblasts (1؋10 5 cells) were treated with P. acnes culture media and formalin-fixed P. acnes (corresponding to 1؋10 6 and 1؋10 7 bacterial cells), the production of proMMP-2 was augmented. In addition, PGN (5-50 m mg/ml) dosedependently augmented the production of proMMP-2 in both cells. Furthermore, the PGN (50 m mg/ml)-augmented proMMP-2 production was resulted from an increase of its transcript. In contrast, there were no changes in cell proliferative activity in either the P. acnes or PGN-treated sebocytes and dermal fibroblasts, indicating that the augmented proMMP-2 production was not due to an increase in cell numbers. Therefore, these results provide novel evidence that PGN transcriptionally up-regulates the production of proMMP-2 in hamster sebocytes and dermal fibroblasts. Given an increase in the quantity of Gram-positive bacteria, including P. acnes in acne lesions, the aberrant ECM degradation may progress in sebaceous glands and pilosebaceous units, which is associated with acne scar formation.

Triptolide suppresses ultraviolet B-enhanced sebum production by inhibiting the biosynthesis of triacylglycerol in hamster sebaceous glands in vivo and in vitro

“…The aggravation of acne is likely to result in a disfiguring and permanent scar formation that carries a psychological and social impact on the patient's quality of life (8,30,31). Allen and LoPresti (32) reported the involvement of sunlight in the aggravation of acne vulgaris, and the current results indicated that triptolide inhibits UVB-enhanced sebaceous TG production in vivo and in vitro.…”

Novel anti‐acne actions of nadifloxacin and clindamycin that inhibit the production of sebum, prostaglandin E2 and promatrix metalloproteinase‐2 in hamster sebocytes

“…In addition, P. acnes has been reported to augment the expression of pro‐MMP‐1/procollagenase‐1 and pro‐MMP‐9/progelatinase B in human monocytes, 8 and that of pro‐MMP‐2/progelatinase A in human dermal fibroblasts 9 . We have also reported that P. acnes and PGN augment the expression of pro‐MMP‐2 in hamster sebocytes 16 …”

“…Hamster sebocytes were cultured in DMEM /F12 supplemented with 6% heat‐denatured fetal bovine serum (JRH Bioscience, Tokyo, Japan), 2% human serum (ICN Biochemicals, Costa Mesa, CA, USA), 0.68 mmol/L l ‐glutamine (Invitrogen, Carlsbad, CA, USA), and recombinant human epidermal growth factor (10 nmol/L) (Progen Biotechnik GmbH, Heidelberg, Germany) as previously described 22 . For PGE 2 and pro‐MMP‐2 production, the cells were treated for 24 h with NDFX (10–50 μg/mL) (kindly provided by Otsuka Pharmaceutical Co., Tokyo, Japan) or CLDM hydrochloride (10–50 μg/mL) (AppliChem GmbH, Darmstadt, Germany) in the presence or absence of PGN (5–50 μg/mL) from Staphylococcus aureus (Sigma Chemical, St Louis, MO, USA) in Dulbecco’s modified Eagle’s medium (DMEM)/F12 supplemented with 0.2% lactalbumin hydrolysate (Sigma Chemical, St Louis, MO, USA) 16,24 . In this series of experiments, hamster sebocytes were used as far as the third passage level.…”

Zinc ascorbate has superoxide dismutase-like activity and in vitro antimicrobial activity against Staphylococcus aureus and Escherichia coli

“…It has been reported that antimicrobial activity of ascorbic acid derivatives on bacterium differs by its species and strains 27. The Gram-positive bacterium S. aureus and Gram-negative bacterium E. coli exist as resident microflora on human skin and are associated with acne development in concert with P. acnes 10–12. Therefore, zinc ascorbate may sufficiently inhibit the growth of S. aureus and E. coli , which participate in acne development in the concentration that is lower than other ascorbic acid derivatives and zinc, similar to its effect on P. acnes 13.…”

“…S. aureus and E. coli exist in the skin lesions of acne patients; they are associated with acne development in concert with P. acnes 10–12. We recently reported that the ascorbic acid derivative zinc ascorbate inhibits the growth of P. acnes in vitro, and it may provide novel insights into acne therapy 13.…”