RESUMO
Acne is a chronic inflammatory illness of the pilosebaceous follicle where innate immunity plays a central role. In acne, the density of Propionibacterium acnes is increased in the pilosebaceous unit. We hypothesized that the severity of acne is not only dependent on the proliferation of P. acnes but also dependent on the pro-inflammatory potential of P. acnes strains and consequently constitutes potential triggering factor for acne scarring. We investigated pro-inflammatory potential of five different strains of P. acnes and P. avidum in skin explants and the preventive effect of zinc gluconate. The expression of immune markers was studied by immunohistochemistry, RT-qPCR and ELISA. P. acnes strains modulate differently the expression of immune markers both at gene and at protein levels. P. acnes type III had the highest pro-inflammatory potential by up-regulating the expression of PAR-2, TNF-alpha, MMP-13 and TIMP-2, whereas P. avidum had the weakest by up-regulating only MMP-13 and TIMP-2. Preincubation of zinc gluconate, which is a modulator of innate immunity, down-regulates the expression of most immune markers induced by P. acnes, PAR-2, TIMP-2, up-regulates MMP-1, TIMP-1. Our results demonstrate that different P. acnes strains have different inflammatory potential targeting markers of cutaneous innate immunity, and that inflammatory potential can be down-regulated by zinc gluconate. As such, the inflammatory potential of P. acnes strains on acne skin may influence the severity of inflammatory acne lesions and scars.
Assuntos
Imunidade Inata , Propionibacterium acnes/imunologia , Propionibacterium acnes/patogenicidade , Pele/imunologia , Pele/microbiologia , Acne Vulgar/etiologia , Acne Vulgar/imunologia , Acne Vulgar/microbiologia , Biomarcadores/metabolismo , Expressão Gênica/efeitos dos fármacos , Gluconatos/farmacologia , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/genética , Mediadores da Inflamação/metabolismo , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Modelos Imunológicos , Propionibacterium acnes/classificação , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Pele/metabolismo , Especificidade da Espécie , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Acne is a chronic inflammatory disease associated with scar development in many patients. OBJECTIVES: To check whether early inflammatory events in the epidermis via keratinocytes influence the development of scars in acne patients. METHODS: We investigated several immunological markers involved in epidermal innate immunity in both clinically normal skin and inflammatory early papules in acne patients prone to scars or not. RESULTS: In normal skin of acne patients prone to scars vs not prone to scars, TLR-4, IL-2, IL-10, TIMP-2 and JUN were significantly overexpressed and the MMP-9 protein level was decreased. Similar results were obtained in early inflammatory papules (no more than three days), except for TLR-4. CONCLUSION: These results suggest for the first time a link between the early events of inflammation with levels of activation of innate immunity in normal epidermis of acne patients and the development of scars. These markers could be a target for drugs in the field of scar prevention.