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Biomedical subjects

Steen Lisby

Publications and source records attributed to Steen Lisby.

7 recordsLinked to original sources
PubMed2006

The autocrine TNFalpha signalling loop in keratinocytes requires atypical PKC species and NF-kappaB activation but is independent of cholesterol-enriched membrane microdomains.

Tumor necrosis factor alpha (TNFalpha) is involved in the pathogenesis of many inflammatory skin diseases. Epidermal keratinocytes produce and respond to TNFalpha via the cognate type 1 receptor (TNFR1). Little is known about regulation of TNFalpha signalling in this cell type. In this study, we report that in keratinocytes TNFalpha upregulates its own mRNA synthesis in an autocrine manner. This response peaks at approximately 1h of stimulation with TNFalpha but sustained elevated levels of TNFalpha mRNA are observed for up to 24h after stimulation and are dependent on the presence of the soluble cytokine. This autocrine response is mediated by the signalling cascade comprising TNFR1, atypical protein kinase C (aPKC) species and the transcription factor NF-kappaB, but is not dependent on the integrity of cholesterol-enriched membrane microdomains (lipid rafts). TNFalpha-stimulated keratinocytes produced the membrane-bound form of TNFalpha. It is conceivable that the described autocrine signalling loop contributes to the proinflammatory TNFalpha effect in the skin. The discovery of the crucial roles of aPKC and NF-kappaB might have consequences for the development of more selective anti-TNFalpha therapies for inflammatory skin diseases.

Antibodies, Monoclonal↗
PubMed2005

UV-induced DNA damage in human keratinocytes: quantitation and correlation with long-term survival.

Ultraviolet (UV) radiation has a major role in the pathogenesis of skin cancer due to its capacity to induce immunosuppression and DNA damage in cells. In this study, we describe the use of a novel extra-long polymerase chain reaction (XL-PCR) assay for detection of UV-inducible DNA lesions in a human keratinocyte line (HaCaT cells). Ultraviolet B (UVB), in doses from 4 to 50 mJ/cm2 resulted in a linear increase in the number of DNA lesions in the genome [range 0.3 +/- 0.2 lesions-3.6 +/- 0.7 lesions (mean +/- SD)/10 kb]. At lower doses of UVB (<10 mJ/cm2), 89 +/- 13% lesions were repaired within 24 h of culture. At higher doses, more lesions remained unrepaired, but the repair efficacy expressed as a proportion of repaired lesions to the total amount of DNA lesions remained constant in the range 0-50 mJ/cm2. Moreover, we demonstrated a correlation between the dose of UV and cell survival. The D37 (dose that reduced clonogenic survival to 37%) of UVB equaled 19 mJ/cm2, corresponding to the introduction of 1.4 lesions/10 kb. In contrast to UVB, UVA1 irradiation neither induced measurable DNA damage nor induced cell death in the doses up to 15 J/cm2. In conclusion, the non-radioactive extra-long (XL)-based real-time (RT)-PCR assay system can be used to quantify the UV-induced DNA damage in intact cells. The DNA lesions detected by this assay are mainly induced by short-waved radiation in the UVB range, and unrepaired DNA lesions cause keratinocyte death or permanent cell-cycle block.

Cell Line, Transformed↗
PubMed2004

Characterization of lymphocyte subpopulations and cytokine profiles in peripheral blood of nickel-sensitive individuals with systemic contact dermatitis after oral nickel exposure.

Several studies have shown that oral nickel exposure can elicit systemic contact dermatitis (SCD) in nickel-sensitive individuals. The current study describes some of the immunological mechanisms underlying such nickel-allergic reactions elicited by oral exposure to nickel. Following oral exposure to graded concentrations of nickel or placebo, blood samples were taken from nickel-sensitive individuals and from non-nickel-sensitive controls. T-cell subtypes (CD3+, CD4+, CD8+ and CD45RO+), expression of skin-homing receptor, cutaneous lymphocyte-associated antigen (CLA) and cytokine profiles [interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, interferon-gamma and tumour necrosis factor-alpha] were investigated. A definite dose-response reaction pattern to oral nickel exposure was observed among nickel-sensitive individuals. Nickel-sensitive individuals whose dermatitis flared after oral challenge with nickel showed significant decreases in fractions of CD3+ CD45RO+ CLA+ and CD8+ CD45RO+ CLA+ blood lymphocytes, suggesting migration of CD8+ 'memory' CLA+ T lymphocytes from the blood to peripheral tissues. Only those nickel-sensitive individuals who clinically reacted to oral challenge with nickel (4 mg) had elevated levels of IL-5 in the serum, indicating an activation of type 2 T lymphocytes in the peripheral blood. In conclusion, the study indicates that CD8+ CD45RO+ CLA+ T lymphocytes and T lymphocytes with a type 2 cytokine profile are involved in SCD elicited by nickel.

Administration, Oral↗
PubMed2003

Release of nickel ions from stainless steel alloys used in dental braces and their patch test reactivity in nickel-sensitive individuals.

Nickel ions leached in sufficient quantities from nickel-containing alloys may induce nickel sensitization or elicit allergic contact dermatitis. Nickel-containing stainless steel alloys are generally considered safe for nickel-sensitive individuals to use. The study summarized in this paper investigated 3 parameters. First, the release of nickel was estimated in artificial saliva and sweat from 4 different stainless steel alloys frequently used in dental braces. Second, in a pilot study, oral mucosa cells harvested from 3 dental patients before and after the attachment of dental braces were analysed for possible nickel content. Third, patch test reactivity of the 4 stainless steel alloys was tested on 31 nickel-sensitive subjects. All 4 stainless steel alloys released small amounts of nickel ions into artificial saliva (<0.13 micro g/cm2/week) and artificial sweat (<0.05 micro g/cm2/week), but no measurable amounts of nickel were found in any of the oral mucosa samples. None of the 31 nickel-sensitive subjects reacted to patch testing with the 4 stainless steel alloys, indicating that these stainless steel alloys would be safe to use in direct and prolonged contact with the skin.

Dental Alloys↗
PubMed2003

Experimental systemic contact dermatitis from nickel: a dose-response study.

Systemic contact dermatitis is usually seen as flare-up of previous dermatitis or de novo dermatitis similar to allergic contact dermatitis. Although systemic contact dermatitis from medicaments is a well-established entity, the existence of clinically relevant systemic reactions to oral nickel exposure, in particular systemic reactions to nickel in the daily diet, remains controversial. Several studies have shown that oral exposure to nickel can induce systemic contact dermatitis in nickel-sensitive individuals. In most of these studies, however, the exposure dose of nickel used has been considerably higher than the nickel content in the normal daily diet. The aim of the current investigation was to study dose-response dependency of oral exposure to nickel. In a double-blind, placebo-controlled oral exposure trial, 40 nickel-sensitive persons and 20 healthy (non-nickel-sensitive) controls were given nickel sulfate hexahydrate in doses similar to and greater than the amount of nickel ingested in the normal Danish daily diet. The nickel content in urine and serum before and after oral exposure was measured to determine nickel uptake and excretion. The influence of the amount of nickel ingested on the clinical reactions to oral exposure and on nickel concentrations in serum and urine was evaluated. Among nickel-sensitive individuals, a definite dose-response dependency was seen, following oral exposure to nickel. 7 of 10 nickel-sensitive individuals had cutaneous reactions to oral exposure to 4.0 mg nickel, an amount approximately 10 times greater than the estimated normal daily dietary intake of nickel. 4 of 10 nickel-sensitive individuals had cutaneous reactions to 1.0 mg nickel, a dose which is close to the estimated maximum amount of nickel contained in the daily diet. 4 of 10 nickel-sensitive individuals reacted to 0.3 mg nickel or to the amount equivalent to that contained in a normal daily diet, and 1 of 10 reacted to a placebo. None of the 20 healthy controls had cutaneous reactions to 4.0 mg nickel or to a placebo. Prior to oral exposure, there was no measurable difference in the amount of nickel in the urine or serum of nickel-sensitive persons and healthy controls. Following the oral challenge, the nickel content in the urine and serum of both nickel-sensitive and healthy control individuals was directly related to the dose of nickel ingested.

Administration, Oral↗