Diana B. Holland

Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses

One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Transfection of TLR2 into a nonresponsive cell line was sufficient for NF-κB activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout, and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes. P. acnes also induced activation of IL-12 p40 promoter activity via TLR2. Furthermore, P. acnes induced IL-12 and IL-8 protein production by primary human monocytes and this cytokine production was inhibited by anti-TLR2 blocking Ab. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for treatment of this common skin disease.

Differential innate immune responses of a living skin equivalent model colonized by staphylococcus epidermidis or staphylococcus aureus

Staphylococcus epidermidis is a commensal on skin, whereas Staphylococcus aureus is a transient pathogen. The aim was to determine whether the skins innate defence systems responded differently to these microorganisms. Differential gene expression of a human skin equivalent (SE) model was assessed by microarray technology, in response to colonization by S. epidermidis or S. aureus. Only a small number of transcripts were significantly (P<0.0001) increased (12) or decreased (35) with gene expression changes of >2-fold on SEs colonized with S. epidermidis compared with controls (no colonization). Expression of one innate defence gene, pentraxin 3 (PTX3), was upregulated, while psoriasin, S100A12, S100A15, beta defensin 4, beta defensin 3, lipocalin 2 and peptidoglycan recognition protein 2 were downregulated. In contrast, large numbers of transcripts were significantly increased (480) or decreased (397) with gene expression changes of >2-fold on SEs colonized with S. aureus compared with controls. There was upregulation in gene expression of many skin defence factors including Toll-like receptor 2, beta defensin 4, properdin, PTX3, proinflammatory cytokines tumour necrosis factor-alpha, IL-1 alpha, IL-1 beta, IL-17C, IL-20, IL-23A and chemokines IL-8, CCL4, CCL5, CCL20 and CCL27. These differences may partly explain why S. epidermidis is a normal skin resident and S. aureus is not.

Propionibacterium acnes and acne.

Acne is a multifactoral disease which is restricted to man and usually presents during and immediately after puberty [1, 2]. The disease is localized to skin regions such as the face, back and chest, with a high number of sebaceous follicles [1, 2] and the condition has been associated with a high sebum excretion rate (SER) [1, 2]. The disease in its various forms and severity is treatable utilizing a range of topical and systemic drugs [1]. The use of cis-retinoic acid to successfully manage severe cases of acne has greatly affected research into the cause of acne and the mechanisms which lead to non-inflamed and inflamed lesions. However, important questions remain unanswered: what causes the variety of the distribution of lesions in patients? what factors are involved in the initiation of inflammation? is Propionibacterium acnes involved in the initiation process? and what mechanisms are involved in the natural regression of the disease in the majority of patients when they reach their mid-twenties? This communication proposes hypotheses, which place P. acnes as an important contributing factor in acne, and it is intended that the hypotheses should provoke increased experimental activity to answer the questions previously listed.

Variation in Pilosebaceous Duct Keratinocyte Proliferation in Acne Patients

The precise pathological processes of comedo formation are not well understood. In patients with acne, there are changes in the process of cornification within the sebaceous follicle. It is thought that an increase in proliferating keratinocytes [1, 2] and their subsequent retention are factors which contribute to this process. In order to investigate the early events involved in the initiation of comedogenesis, normal follicles from acne patients have been labelled using immunohistochemistry with antibodies to Ki-67 and keratin 16 (K16). Ki-67 is a non-histone protein which labels all cycling cells except those in G0, whereas K16 is a protein which is up-regulated in all abnormally differentiating and hyperproliferating suprabasal keratinocytes. Patients and Methods

Detection of Propionibacterium acnes polypeptides which have stimulated an immune response in acne patients but not in normal individuals

Abstract Patient and normal volunteer sera were used as probes in two‐dimensional PAGE of P. acnes culture supernatant fluid and cell extracts to determine whether specific P. acnes polypeptides were associated with the immune reaction in acne. Eight polypeptides, Mr 20 to 131 × 103, pi 4.7 to 6.5 in the cell extract, and 7 polypeptides Mr 10 to 24 kD, pI 4.8 to 7.5 in the culture supernatant fluid were specifically highlighted by patient sera and not volunteer sera. These polypeptides were not related to described extracellular enzymes of P. acnes. It is possible that these polypeptides are involved in the induction of acne.

Investigation of the mechanism of action of 2% fusidic acid lotion in the treatment of acne vulgaris.

We describe the results of a single‐centre, double‐blind, vehicle‐controlled, parallel group study on the quantitative effects of 2% fusidic acid lotion (Fucidin® lotion) in facial acne vulgaris. The trial was completed by 52 patients aged 15–25 years with mild to moderate acne who had been randomized to either Fucidin® Lotion (n= 25) or its base (n= 27).