ABSTRACT
Propionibacterium acnes plays an important role in the pathogenesis of acne and it is established that this bacteria is involved in the induction and maintenance of the inflammatory phase of acne. The aim of our work was to determine if P. acnes extracts could modulate integrins and filaggrin in vitro expression by keratinocytes. Integrins and filaggrin expression was examined using immunohistochemistry technique both on Normal Human Epiderminal Keratinocytes (NHEK) and on deep-frozen sections of normal human skin explants incubated with three different P. acnes extracts. In addition, the expression of filaggrin was investigated on biopsies of acne lesions and by western-blot associated with its precursor profilaggrin. We demonstrated that P. acnes extracts induced beta1 integrin expression significantly on both proliferating keratinocytes and differentiated keratinocytes. In addition, P. acnes induced alpha3, alpha6s and alphaVbeta6 integrin expression and filaggrin expression on differentiated keratinocytes. Finally P. acnes extracts increased filaggrin expression by suprabasal layer of epidermis of explants. Western-blot confirmed that total amount of filaggrin was increased. These results indicate that P. acnes extracts are directly able to modulate the differentiation of keratinocytes suggesting that this bacteria play a role not only in the development of inflammatory acne lesions but also in the formation of the microcomedo.
Subject(s)
Acne Vulgaris/metabolism , Integrins/metabolism , Intermediate Filament Proteins/metabolism , Keratinocytes/metabolism , Propionibacterium acnes , Skin/metabolism , Subcellular Fractions , Acne Vulgaris/microbiology , Acne Vulgaris/pathology , Antigens, Neoplasm/metabolism , Blotting, Western , Cell Differentiation , Cell Proliferation , Cells, Cultured , Filaggrin Proteins , Humans , Immunohistochemistry , Integrin alpha3/metabolism , Integrin alpha6/metabolism , Integrin beta1/metabolism , Keratinocytes/microbiology , Keratinocytes/pathology , Organ Culture Techniques , Skin/microbiology , Skin/pathologyABSTRACT
The aim of this work was to study Toll-like receptors (TLRs) 2, 4 and 9 expression patterns in parapsoriasis and in cutaneous T-cell lymphoma (CTCL): Mycosis fungoides (MF) and Sézary syndrome (SS) at different stages of the illness. The expression of TLRs was examined by immunohistochemistry on paraffin-embedded biopsies. Normal skin, atopic dermatitis and psoriasis, were used as controls. In cutaneous lesions of inflammatory diseases (atopic dermatitis, psoriasis) the expression of TLR2, TLR4 and TLR9 was low compared to normal skin. In parapsoriasis the expression of the three TLRs was similar to control. By contrast, in MF skin we observed a strong intensity of labelling with the three TLRs in the epidermis. Concerning SS, the expression of TLR2, TLR4 and TLR9 was intermediate between inflammatory lesions and MF. Thus, the development of skin lesions in MF appears associated with an increase of TLR2, TLR4 and TLR9 expression by keratinocytes in cutaneous lesions, which could play a role in the chronic activation of T lymphocytes in the skin.
Subject(s)
Lymphoma, T-Cell, Cutaneous/immunology , Skin Neoplasms/immunology , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 9/metabolism , Biopsy , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Lymphoma, T-Cell, Cutaneous/pathology , Mycosis Fungoides/immunology , Mycosis Fungoides/pathology , Sezary Syndrome/immunology , Sezary Syndrome/pathology , Skin/immunology , Skin/pathology , Skin Neoplasms/pathology , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Toll-Like Receptor 9/geneticsABSTRACT
BACKGROUND: The bacterium Propionibacterium acnes is involved in the induction and maintenance of the inflammatory phase of acne. Recent studies have found that keratinocytes express toll-like receptors (TLRs) implicated in immediate immunity. No studies have, to date, been carried out on the action of P. acnes upon TLR activation in keratinocytes. OBJECTIVES: Focusing on the inflammatory phase of acne, to clarify the role of P. acnes in immediate immunity by inducing expression of TLR-2 and TLR-4 by keratinocytes. We also studied how the secretion and expression of matrix metalloproteinase (MMP)-9 is induced by P. acnes. METHODS: The work was carried out on two levels: in vivo with the study of the expression of TLR-2 and TLR-4 proteins in biopsies of acne lesions and in vitro on cultured keratinocyte monolayers to study the modulating effects of P. acnes on the expression of TLR-2 and TLR-4 and also on the expression and secretion of MMP-9. RESULTS: Our findings reveal that in vivo TLR-2 and TLR-4 expression is increased in the epidermis of acne lesions. In vitro, an increase in TLR-2 and TLR-4 expression by human keratinocytes occurred in the first hours of incubation with bacterial fractions as well as an increase of the expression and secretion by the keratinocytes of MMP-9, which plays a role in inflammation. CONCLUSIONS: This work demonstrates that P. acnes induces TLR expression and that this mechanism could play an essential role in acne-linked inflammation. These receptors could be involved notably in acute acne.
