Immune response profiling of primary monocytes and oral keratinocytes to different Tannerella forsythia strains and their cell surface mutants.

The oral pathogen Tannerella forsythia possesses a unique surface (S-) layer with a complex O-glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. forsythia strains ATCC 43037 and UB4 displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay. When challenged with T. forsythia, monocytes secrete proinflammatory cytokines, chemokines and vascular endothelial growth factor (VEGF) with the release of interleukin-1ß (IL-1ß) and IL-7 being differentially regulated by the two T. forsythia wild-type strains. Truncation of the bacteria's O-glycan leads to significant reduction of IL-1ß and regulates macrophage inflammatory protein-1. HOK infected with T. forsythia produce IL-1Ra, chemokines and VEGF. Although the two wild-type strains elicit preferential immune responses for IL-8, both truncation of the O-glycan and deletion of the S-layer result in significantly increased release of IL-8, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1. Through immunofluorescence and confocal laser scanning microscopy of infected HOK we additionally show that T. forsythia is highly invasive and tends to localize to the perinuclear region. This indicates, that the T. forsythia S-layer and attached sugars, particularly pseudaminic acid in ATCC 43037, contribute to dampening the response of epithelial tissues to initial infection and hence play a pivotal role in orchestrating the bacterium's virulence.

[Friend or Foe?--Psoriasin and Koebnerisin: multifunctional defence molecules in skin differentiation, tumorigenesis and inflammation]. / Friend or Foe?--Psoriasin und Koebnerisin.

Psoriasin (S100A7) and koebnerisin (S100A15) were first identified in inflamed psoriatic skin. They have lately evolved by gene duplications within the Epidermal Differentiation Complex (chromosome 1q21) and form a novel S100 subfamily in human. Despite highest homology (>  90 %), psoriasin and koebnerisin are distinct in tissue distribution, regulation, and function. They act differently as antimicrobial peptides (AMP) and synergize to promote inflammation and cell migration as endogenous danger signals ("alarmines") and chemoattractants. Their different properties are compelling reasons to discriminate psoriasin and koebnerisin in epithelial homeostasis, inflammation and epithelial carcinogenesis.

Proliferative response of human prostate tumour xenografts to surgical trauma and the transurethral resection of the prostate controversy.

Transurethral resection of the prostate (TURP) as an excisional procedure involving multiple incisions into the prostate does not differentiate between palpably benign prostate tissue and microscopic foci of well-differentiated adenocarcinoma. The impact of TURP on the progression of such 'latent' or 'incidental' tumours unique to the prostate gland has been a focal point of a continuing controversy. In studies designed to develop preclinical evidence that would lend support to, or detract from, either side of the TURP controversy, surgical trauma-induced stimulation of in situ tumour growth was extended to include human prostate tumour tissue PC-3, DU-145 and H-1579, albeit as xenografts in athymic nude males. A significant proliferative response of prostate tumours implanted directly in, adjacent to, or distant from, a freshly induced surgical wound, could be inhibited by a somatostatin analogue (Lanreotide) applied topically to the surgical site. This preclinical model supports TURP as a risk factor for biopsy or therapeutic surgical intervention procedures in benign prostatic hypertrophy (BPH), a risk factor that increases with the stage of disease in undetected cancers. It also suggests a potential clinical benefit that might be derived by applying Lanreotide directly to the surgically traumatised genitourinary area by simple irrigation of the urethra and bladder during or shortly post TURP.