PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes

Danis, Judit; Göblös, Anikó; Bata‐Csörgő, Zsuzsanna; Kemény, Lajos; Széll, Márta

doi:10.3389/fimmu.2017.01053

Cited by 25 publications

(27 citation statements)

References 37 publications

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“…Previously, we reported that Der p did not trigger the phosphorylation of IκBα, while poly I:C, which is structurally similar to double‐stranded RNA, did . In addition, TLR9 responds to single‐stranded DNA . No phosphorylation of IκBα was observed in keratinocytes treated with or without heparinoid in this study.…”

Section: Discussioncontrasting

confidence: 47%

Heparinoid suppresses Der p‐inducedIL‐1β production by inhibitingERKand p38MAPKpathways in keratinocytes

Utsunomiya

Dai

Murakami

et al. 2018

Experimental Dermatology

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Epidermal keratinocytes initiate skin inflammation by activating immune cells. The skin barrier is disrupted in atopic dermatitis (AD) and epidermal keratinocytes can be exposed to environmental stimuli, such as house dust mite (HDM) allergens. We showed previously that HDM allergens activate the NLRP3 inflammasome of keratinocytes, thereby releasing pro-inflammatory cytokines. Heparinoid is an effective moisturizer for atopic dry skin. However, a recent report showed that heparinoid treatment can improve inflammation of lichen planus. Therefore, we hypothesized that it acts on epidermal keratinocytes not only as a moisturizer, but also as a suppressant of the triggers of skin inflammation. We found that HDM allergen-induced interleukin (IL)-1β release from keratinocytes was inhibited significantly by heparinoid pretreatment without affecting cell viability. However, heparinoid did not affect caspase-1 release, suggesting that heparinoid did not affect HDM allergen-induced inflammasome activation. Heparinoid treatment not only decreased intracellular levels of pro-IL-1β, but also suppressed IL-1β messenger RNA (mRNA) expression in keratinocytes. Among the intracellular signalling pathways, the activation of extracellular signal-regulated kinase and p38 pathways, which are required for IL-1β expression in keratinocytes, was inhibited by heparinoid treatment. The inhibitory effect of heparinoid on IL-1β mRNA expression was also confirmed with living skin equivalents. Our results demonstrated that heparinoid suppresses the initiation of keratinocyte-mediated skin inflammation.

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Section: Discussioncontrasting

confidence: 47%

Heparinoid suppresses Der p‐inducedIL‐1β production by inhibitingERKand p38MAPKpathways in keratinocytes

Utsunomiya

Dai

Murakami

et al. 2018

Experimental Dermatology

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“…The study was approved by the Human Investigation Review Board of the University of Szeged (PSO-EDAFN-002, 23 February 2015, Szeged, Hungary) and complying with the ethical standards in accordance with the Helsinki Declaration. NHEK cells were isolated from the skin samples as described earlier ( 24 ). For ex vivo organotypic skin models (OSMs), 6 mm punch biopsies were washed first with normal saline solution (NSS) containing 2% AB/AM, followed by a wash in AB/AM-free NSS.…”

Section: Methodsmentioning

confidence: 99%

TNIP1 Regulates Cutibacterium acnes-Induced Innate Immune Functions in Epidermal Keratinocytes

et al. 2018

Self Cite

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Human skin cells recognize the presence of the skin microbiome through pathogen recognition receptors. Epidermal keratinocytes are known to activate toll-like receptors (TLRs) 2 and 4 in response to the commensal Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes) bacterium and subsequently to induce innate immune and inflammatory events. These events may lead to the appearance of macroscopic inflammatory acne lesions in puberty: comedos, papules and, pustules. Healthy skin does not exhibit inflammation or skin lesions, even in the continuous presence of the same microbes. As the molecular mechanism for this duality is still unclear, we aimed to identify factors and mechanisms that control the innate immune response to C. acnes in keratinocytes using a human immortalized keratinocyte cell line, HPV-KER, normal human keratinocytes (NHEK) and an organotypic skin model (OSM). TNIP1, a negative regulator of the NF-κB signaling pathway, was found to be expressed in HPV-KER cells, and its expression was rapidly induced in response to C. acnes treatment, which was confirmed in NHEK cells and OSMs. Expression changes were not dependent on the C. acnes strain. However, we found that the extent of expression was dependent on C. acnes dose. Bacterial-induced changes in TNIP1 expression were regulated by signaling pathways involving NF-κB, p38, MAPKK and JNK. Experimental modification of TNIP1 levels affected constitutive and C. acnes-induced NF-κB promoter activities and subsequent inflammatory cytokine and chemokine mRNA and protein levels. These results suggest an important role for this negative regulator in the control of bacterially induced TLR signaling pathways in keratinocytes. We showed that all-trans retinoic acid (ATRA) induced elevated TNIP1 expression in HPV-KER cells and also in OSMs, where TNIP1 levels increased throughout the epidermis. ATRA also reduced constitutive and bacterium-induced levels of TNFα, CCL5 and TLR2, while simultaneously increasing CXCL8 and TLR4 expression. Based on these findings, we propose that ATRA may exhibit dual effects in acne therapy by both affecting the expression of the negative regulator TNIP1 and attenuating TLR2-induced inflammation. Overall, TNIP1, as a possible regulator of C. acnes-induced innate immune and inflammatory events in keratinocytes, may play important roles in the maintenance of epidermal homeostasis.

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“…The genes transcribed within a 100 kb window upstream or downstream of lncRNAs were considered as potential cis target genes [79]. The second algorithm was used to identify potential trans targets based on RNA sequence complementarity (mRNA-lncRNA) and RNA duplex energy prediction [80,81]. Based on the RNA duplex energy (Free energy < − 50) assessed by RIsearch algorithms [82], the differentially expressed genes and lncRNAs were considered as potentially involved in trans-interaction.…”

Section: Target Gene Prediction and Functional Analysis Of Lncrnasmentioning

confidence: 99%

Global identification and analysis revealed differentially expressed lncRNAs associated with meiosis and low fertility in autotetraploid rice

Shahid

Wen

et al. 2020

BMC Plant Biol

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Background: Autotetraploid rice is a useful germplasm for polyploid rice breeding. Our previous research showed that non-coding RNAs might be associated with low fertility in autotetraploid rice. However, little information is available on long non-coding RNAs (lncRNAs) involved in the low fertility of autotetraploid rice. In the present study, RNA-seq was employed to detect the differentially expressed meiosis-related lncRNAs in autotetraploid rice, and gene overexpression and knock out experiments were used to validate the potential function of candidate lncRNA. Results: A total of 444 differentially expressed lncRNAs (DEL) were detected during anther and ovary meiosis in autotetraploid rice. Of these, 328 DEL were associated with the transposable elements, which displayed low expression levels during meiosis in autotetraploid rice. We used rapid amplification of cDNA ends (RACE) assay to validate 10 DEL and found that the lncRNAs were not assembly artifacts, and six of them were conserved in tetraploid rice. Moreover, 237 and 20 lncRNAs were associated with pollen mother cell (PMC) and embryo sac mother cell (EMC) meiosis in autotetraploid rice, respectively. The differential expressions of some meiosis-related targets and its DEL regulator, including MEL1 regulated by TCONS_00068868, LOC_Os12g41350 (meiotic asynaptic mutant 1) by TCONS_00057811 in PMC, and LOC_Os12g39420 by TCONS_00144592 in EMC, were confirmed by qRT-PCR. TCONS_00057811, TCONS_00055980 and TCONS_00130461 showed anther specific expression patterns and were found to be highly expressed during meiosis. CRISPR/Cas9 editing of lncRNA57811 displayed similar morphology compared to wild type. The overexpression of lncRNA57811 resulted in low pollen fertility (29.70%) and seed setting (33%) in rice. Conclusion: The differential expression levels of lncRNAs, associated with transposable elements and meiosisregulated targets, might be endogenous noncoding regulators of pollen/embryo sac development that cause low fertility in autotetraploid rice. The results enhance our understanding about rice lncRNAs, and facilitate functional research in autotetraploid rice.

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PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes

Cited by 25 publications

References 37 publications

Heparinoid suppresses Der p‐inducedIL‐1β production by inhibitingERKand p38MAPKpathways in keratinocytes

Heparinoid suppresses Der p‐inducedIL‐1β production by inhibitingERKand p38MAPKpathways in keratinocytes

TNIP1 Regulates Cutibacterium acnes-Induced Innate Immune Functions in Epidermal Keratinocytes

Global identification and analysis revealed differentially expressed lncRNAs associated with meiosis and low fertility in autotetraploid rice

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