54 research outputs found
Investigations on cytosolic nucleic acid fragment induced innate immune functions of keratinocytes
In this study, we characterized the dsRNA and dsDNA induced immune responses in human keratinocytes by studying pre- and posttranscriptional regulation of cytokine expression.
• We compared the dsRNA and dsDNA induced cytokine expression in three keratinocyte cell types: NHEKs, HaCaT cells and HPV-KER cells. We found that transfection by the synthetic dsRNA and dsDNA analogue poly(I:C) and poly(dA:dT) induce the expression of IL-6 and TNF-α with notable kinetic differences and rate of induction.
• We found that poly(I:C) and poly(dA:dT) induce the same inflammatory signaling pathways in keratinocytes, albeit with different kinetics and magnitude of activation. Our data revealed that transfection with poly(I:C) and poly(dA:dT) induced activation of NF-κB and STAT signaling, which along with p38 signaling were also shown to be functional in inducing cytokine mRNA expression. We also showed the negative regulatory role of ERK1/2 signaling in nucleotide-induced IL-6 mRNA expression in keratinocytes, which seems to be a celltype specific event.
• By studying the expression pattern of PRINS lncRNA, we found decreased expression upon poly(dA:dT) transfection in NHEKs, while poly(I:C) did not led to altered expression of PRINS.
• We have identified a potential negative regulatory role for PRINS lncRNA in poly(dA:dT) induced IL-6 and CCL-5 expression. In-depth analysis of this phenomenon revealed the sequence specific interaction between PRINS and the mRNA of IL-6 and CCL-5, which might be responsible for the posttranscriptional control of the mRNA expression. These results led us to hypothesize, that elevated PRINS expression in psoriatic uninvolved epidermis may contribute to downregulation of the inflammatory functions in psoriatic keratinocytes and maintenance of the normal phenotype
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Validation of the Mothers’ Object Relations Scales Short-form (MORS-SF)
A 14-item questionnaire, MORS-SF, was developed in a previous study to assess mothers’ representations of their infants. It was found to have good psychometric properties, being sufficiently reliable and internally valid to enable the further validation of the instrument with additional independently collected datasets. This paper reports the successful validation of MORS-SF against other measures in both the original Hungarian and British samples and also in new samples in both countries, showing predicted relationships with other measures in the original and the independent validation datasets. It is concluded that this is a valid tool, with uses in research and health practice
Recommended from our members
Validation of the Mothers’ Object Relations Scales Short-form (MORS-SF)
A 14-item questionnaire, MORS-SF, was developed in a previous study to assess mothers’ representations of their infants. It was found to have good psychometric properties, being sufficiently reliable and internally valid to enable the further validation of the instrument with additional independently collected datasets. This paper reports the successful validation of MORS-SF against other measures in both the original Hungarian and British samples and also in new samples in both countries, showing predicted relationships with other measures in the original and the independent validation datasets. It is concluded that this is a valid tool, with uses in research and health practice
A telemedicina alkalmazása a bőrgyógyászatban: a teledermatológia
Absztrakt
Az utóbbi évtizedek telekommunikációs és informatikai-technológiai fejlődése az
egészségügyi ellátásban is jelentős változásokat hozott, és kialakult az
orvostudomány új ága, a telemedicina. Az elmúlt 20 évben a telekommunikációs
hálózatok folyamatos fejlődése, az internet megjelenése, az okostelefonok
térhódítása lehetővé tette a telemedicina ugrásszerű fejlődését, így mára már
számos eszköz és alkalmazás áll rendelkezésünkre, ezzel párhuzamosan pedig a
szakirodalmi publikációk és hivatkozások száma is exponenciálisan növekszik. A
terület egyik legdinamikusabban fejlődő ágává a teledermatológia, azaz a
telemedicina bőrgyógyászati alkalmazása vált, mivel a bőrön található
elváltozások jól láthatóak és hozzáférhetőek, az új eszközökkel pedig komolyabb
beavatkozás nélkül is dokumentálhatóak. A módszer Magyarországon eddig még nem
honosodott meg, pedig alkalmazásával a betegellátás hatékonyabbá, gyorsabbá és
olcsóbbá válhat. A szerzők célja, hogy áttekintsék a bőrgyógyászat
távkonzultációs gyakorlatának külföldi tapasztalatait és legfontosabb
eredményeit. Kiemelik a teledermatológia jellegzetességeit, a vizsgálatok
megbízhatóságát, a módszer ellátórendszerre gyakorolt hatását, valamint a
szubjektív és objektív előnyöket és hátrányokat. Orv. Hetil., 2016,
157(10), 363–369
THE NON-CODING RNA, PRINS AFFECTS AIM2 INFLAMMASOME ACTIVATION IN KERATINOCYTES
The non-coding RNA, PRINS was previously described by our research group as a differentially expressed transcript in psoriatic uninvolved and healthy skin. The expression level of PRINS in cultured keratinocytes is altered after exposure to various stress factors and silencing of it decreases the viability of keratinocytes during stress stimulations suggesting its role in stress response of the cells. A potential stress signal in psoriatic skin may be the extracellular DNA, which activates the AIM2 inflammasome. The activated inflammasome cleaves the precursor proIL-1β form into mature, functioning IL-1β. The role of the AIM2 inflammasome and the IL-1β cytokine in psoriasis has been described recently.
The aim of our study was to investigate if the PRINS non coding RNA affects the expression and activation of the inflammasome members and IL-1β in normal human epidermal keratinocytes (NHEK) after exposure to extracellular DNA.
The expression of PRINS was transiently silenced by a vector based RNA interference method in cultured NHEK cells. Silenced and non-silenced NHEK cells were primed with the cytokines TNF-α and IFN-γ and transfected with the synthetic DNA analogue poly(dA:dT). The expression of PRINS and inflammasome members was detected by real-time RT-PCR and the secreted IL-1β was measured by ELISA.
Poly(dA:dT) treatment caused a moderate increase in PRINS expression and IL-1β secretion as well, whereas priming with a combination of TNF-α and IFN-γ before poly(dA:dT) transfection resulted in a highly elevated PRINS expression and higher secreted IL-1β levels. The silencing of PRINS decreased the amount of secreted IL-1β, but did not affect the expression of the proIL-1β or AIM2.
Our results suggest that the PRINS non-coding RNA regulates the IL-1β production of NHEK cells, but not through the regulation of proIL-1β expression, rather contributing to inflammasome-activation
Genodermatózisok kutatása a szegedi Bőrgyógyászati és Allergológiai Klinikán [Research in genodermatoses at the Szeged Department of Dermatology and Allergology]
Molecular differences of NLRP3 inflammasome activation in LPS-activated human monocyte-derived macrophage subtypes
Psoriasis-Associated Inflammatory Conditions Induce IL-23 mRNA Expression in Normal Human Epidermal Keratinocytes
Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene
Spinocerebellar ataxia (SCA) 40 is an extremely rare subtype of the phenotypically and genetically diverse autosomal dominant ataxias caused by mutations of the CCDC88C gene. Most reported cases of SCA40 are characterized by late-onset cerebellar ataxia and variable extrapyramidal features; however, there is a report of a patient with early-onset spastic paraparesis as well. Here, we describe a novel missense CCDC88C mutation (p.R203W) in the hook domain of the DAPLE protein encoded by the CCDC88C gene that was identified in a female patient who developed late-onset ataxia, dysmetria and intention tremor. To explore the molecular consequences of the newly identified and previously described CCDC88C mutations, we carried out in vitro functional tests. The CCDC88C alleles were expressed in HEK293 cells, and the impact of the mutant DAPLE protein variants on JNK pathway activation and apoptosis was assessed. Our results revealed only a small-scale activation of the JNK pathway by mutant DAPLE proteins; however, increased JNK1 phosphorylation could not be detected. Additionally, none of the examined mutations triggered proapoptotic effect. In conclusion, we identified a novel mutation of the CCDC88C gene from a patient with spinocerebellar ataxia. Our results are not in accord with previous observations and do not support the primary role of the CCDC88C mutations in induction of JNK pathway activation in ataxia. Therefore, we propose that CCDC88C mutations may exert their effects through different and possibly in much broader, yet unexplored, biological processes
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