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Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway

ABSTRACT: Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway

PROVIDER: PRJNA1294752 | ENA |

REPOSITORIES: ENA

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Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway

Project description:Rosacea is a chronic inflammatory disease of facial skin with unknown pathophysiology. Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea. However, its significance in the rosacea pathogenesis is not fully understood. We sought to understand the molecular mechanisms of LL-37-mediated rosacea-like inflammation in an in-vitro model of normal human epidermal keratinocytes. Transcriptome profiling of LL-37-treated keratinocytes identified signatures of interferon (IFN)-stimulating genes (ISGs) such as CXCL10, IFIT2, RSAD2 and CXCL11 among the top upregulated differentially expressed genes. Gene ontogeny (GO) enrichment of biological processes revealed activation of cellular response to molecules of bacterial origin, response to chemokines, and cytokine mediated signaling pathways. While KEGG enrichment analysis revealed the activation of TNF signaling, IL-17 signaling, NF-kB signaling and chemokine signaling among the most significant pathways. Remarkably, T cell recruiting chemokine CXCL10 turns out to be the most abundant inflammatory mediator overexpressed upon LL-37 exposure. Mechanistically, LL-37 induced CXCL10 production relied on JAK-1/STAT-1 signaling pathway. In summary, our findings provide a crucial link to keratinocyte: T cell crosstalk and blockade of CXCL10:CXCR3 axis or JAK-1/STAT-1 pathways can be an effective anti-inflammatory strategy to reduce rosacea inflammation by restricting pathogenic T cells infiltration.

2025-07-22 | GSE303282 | GEO

The human cathelicidin antimicrobial peptide LL-37 promotes the growth of the pulmonary pathogen Aspergillus fumigatus.

Project description:Aspergillus fumigatus contributes to invasive and allergic pulmonary disease in immunocompromised individuals. The pulmonary mucus of cystic fibrosis (CF) patients displays elevated levels of the pleiotropic cathelicidin antimicrobial peptide LL-37 and the aim of this work was to assess the effect of LL-37 on the growth A. fumigatus. Exposure of A. fumigatus conidia to high concentrations of intact LL-37 (100 μg/ml) for 24 hours had a positive effect on growth (277.45 ± 22.59% (p < 0.01)) whereas scrambled LL-37 (76.45 ± 7.46%) did not. Exposure of 24 hour pre-formed mycelium to 5 μg/ml LL-37 for 48 hours increased hyphal wet weight significantly (4.37 ± 0.23 g, p < 0.001) compared to the control (2.67 ± 0.05 g). Amino acid leakage from mycelium was observed in the presence of LL-37 and gliotoxin secretion was increased at 24 hours from LL-37 exposed hyphae (169.1 ± 6.36 ng/mg hyphae, p < 0.05) compared to the control (102 ± 18.81 ng/mg hyphae). Quantitative proteomic analysis of 24 hour LL-37 treated hyphae revealed an increase in the abundance of proteins associated with growth (eIF-5A (16.3 fold increased), tissue degradation (aspartic endopeptidase (4.7 fold increased)) and allergic reactions (Asp F13 (10 fold increased)). By 48 hours there was an increase in proteins indicative of cellular stress (glutathione peroxidase (9 fold increased)), growth (eIF-5A (6 fold increased), and virulence (ribonuclease mitogillin (3.7 fold increased). These results indicate that LL-37 stimulates A. fumigatus growth and this may result in increased fungal growth and secretion of toxins in the lungs of CF patients.

2018-05-22 | PXD008143 | Pride

A positive feedback circuit between mTORC1 signaling and cathelicidin promotes skin inflammation in rosacea [mouse]

Project description:The goal of this study is to figure out the role of mTORC1 signaling in the pathogenesis of rosacea by comparing rosacea mouse model skin lesion transcriptome profiling (RNA-seq) to that of control mouse skin treated with or without rapamycin.

2021-02-08 | GSE147950 | GEO

A positive feedback circuit between mTORC1 signaling and cathelicidin promotes skin inflammation in rosacea [mouse]

Project description:A positive feedback circuit between mTORC1 signaling and cathelicidin promotes skin inflammation in rosacea [mouse]

| PRJNA622593 | ENA

Melanoma-derived exosomal miRNAs and keratinocyte-derived LL-37 define an epidermal–tumor arms race in melanoma

Project description:Melanoma progression involves dynamic interactions between tumor cells and the surrounding epidermal microenvironment. The cathelicidin antimicrobial peptide LL-37, expressed by keratinocytes, has been implicated in tumor-host defense; however, its transcriptomic impact on melanoma cells and its in vivo relevance remain incompletely characterized. Here, we performed bulk RNA sequencing of LL-37-treated A375 human melanoma cells in vitro and of tumor-bearing dorsal skin from K14CreCampf/f (cKO) and wild type mice (WT) subjected to topical imiquimod stimulation in vivo, to elucidate the transcriptomic landscape underlying LL-37-mediated suppression of melanoma progression.

2026-07-22 | GSE334049 | GEO

Th1/Th17 Immune Response in Rosacea

Project description:Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, qRT-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFNγ or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, while neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern towards phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration is an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.

2015-06-01 | GSE65914 | GEO

Ducula rosacea

Project description:Ducula rosacea

| PRJNA852984 | ENA

Transcription profiling of three cutaneous rosacea subtypes to characterize the inflammatory infiltrate

Project description:Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, qRT-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFNÎ³ or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, while neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern towards phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration is an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease. Total of 58 chips. 19 patients and 10 healthy volunteers

2015-06-01 | E-GEOD-65914 | biostudies-arrayexpress

RNA-seq analysis of growth factor response of NHEKs to antimicrobial petide LL-37 and dsRNA mimic Poly(I:C)

Project description:In this study, we analyzed how non-coding double stranded RNA (dsRNAs) act as a damage associated molecular pattern (DAMP) in the skin, and how the human cathelicidin AMP LL-37 might influence growth factor production in response to this DAMP.

2016-05-23 | GSE79343 | GEO

Transcriptome analysis of Streptococcus suis upon exposure to sub-lethal concentrations of LL-37

Project description:Streptococcus suis is a major pig pathogen as well as an emerging zoonotic pathogen. We studied the generic and adaptive resistance response of S. suis upon exposure to sub-lethal concentrations of the human cathelicidin LL-37. We aimed to search for inducible mechanisms of resistance to AMPs as well as induction of virulence gene expression upon exposure to AMPs, in order to gain insights into host-derived factors that might mediate S. suis pathogenesis.

2022-09-01 | GSE92503 | GEO

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