Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Age-related loss of innate immune antimicrobial function of dermal fat is mediated by TGFβ

ABSTRACT: Dermal fibroblasts (dFB) resist infection by locally differentiating into adipocytes and producing the antimicrobial peptide cathelicidin in response to S. aureus. We found that neonatal dFB were highly adipogenic whereas this adipogenic function was lost during adulthood. To better understand the molecular nature of the change in antimicrobial and adipogenic function of dFB, we profiled the transcriptomes of primary dFB isolated at different ages by RNA-seq. RNA-seq identified the pro-adipogenic to pro-fibrotic gene signature switch in dFB during aging, and identified TGF-beta as the top up-regulated pathway that was activated in 2M dFB compared to neonatal P1 dFB.

ORGANISM(S): Mus musculus

PROVIDER: GSE121460 | GEO | 2018/10/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne

Project description:Innate immune defense against deep tissue infection by Staphylococcus aureus is orchestrated by fibroblasts that become antimicrobial when triggered to differentiate into adipocytes. However, the role of this process in non-infectious human diseases is unknown. To investigate the potential role of adipogenesis by dermal fibroblasts in acne, a disorder triggered by Cutibacterium acnes (C. acnes), single-cell RNA-sequencing was performed on human acne lesions and mouse skin challenged by C. acnes. A transcriptome consistent with adipogenesis was observed within specific fibroblast subsets from human acne and mouse skin lesions infected with C. acnes. Perifollicular dermal preadipocytes in human acne and mouse skin lesions showed colocalization of PREF1, an early marker of adipogenesis, and cathelicidin (Camp), an antimicrobial peptide. This capacity of C. acnes to trigger production of cathelicidin in preadipocytes was dependent on TLR2. Treatment of wild-type mice with retinoic acid (RA) suppressed the capacity of C. acnes to form acne-like lesions, inhibited adipogenesis and enhanced cathelicidin expression in preadipocytes, but lesions were unresponsive in Camp-/- mice, despite the anti-adipogenic action of RA. Analysis of inflamed skin of acne patients after retinoid treatment also showed enhanced induction of cathelicidin, a previously unknown beneficial effect of retinoids in difficult-to-treat acne. Overall, these data provide evidence that adipogenic fibroblasts are a critical component of the pathogenesis of acne and represent a potential target for future therapy.

2022-01-16 | GSE193584 | GEO

Human cathelicidin antimicrobial peptide LL37 effect on human neonatal epidermal keratinocytes (NHEKs).

Project description:Analysis of undifferentiated keratinocytes or differentiated keratinocytes stimulated with or without human cathelicidin antimicrobial peptide (CAMP) LL37. Results provide insight into the biological effects of CAMP on human keratinocytes. NHEKs were divided into two groups; low calcium (0.05 mM) and high calcium condition (1.6 mM). Then keratinocytes were stimulated with human cathelicidin antimicrobial peptide LL37 at 0, 2.56, and 7.68 M-NM-<M for 12 h to 24 h.

2014-08-01 | E-GEOD-49472 | biostudies-arrayexpress

Human cathelicidin antimicrobial peptide LL37 effect on human neonatal epidermal keratinocytes (NHEKs).

2014-08-01 | GSE49472 | GEO

Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

2007-09-01 | GSE8921 | GEO

Cathelicidin-deficient mice exhibit increased survival and upregulation of key inflammatory response genes following cecal ligation and puncture

Project description:Antimicrobial peptides possess a myriad of molecular properties including bacterial killing and the regulation of many aspects of innate immunity. Cathelicidins are a group of antimicrobial peptides widely investigated by the scientific community. Many studies have focused on the bactericidal and pro-inflammatory roles of cathelicidins. Because the role of endogenous cathelicidin expression remains obscure in deep-seated systemic infections, we induced sepsis in cathelicidin knockout and wild-type (WT) mice by cecal ligation and puncture, performing transcriptome screening by DNA microarray in conjunction with other immunologic assays. Cathelicidin-deficient mice showed increased survival compared to WT mice in this established experimental model of polymicrobial sepsis, in association with upregulation of certain key inflammatory response genes. Therefore, cathelicidins can exert both pro- and anti-inflammatory activities depending on the disease and cellular context.

2017-06-20 | GSE90727 | GEO

The antimicrobial peptide-sensing system aps of Staphylococcus aureus

Project description:Staphylococcus aureus is a leading cause of hospital-associated infections. In addition, highly virulent strains of methicillin-resistant S. aureus (MRSA) are currently spreading outside health care settings. Survival in the human host is largely defined by the ability of S. aureus to resist mechanisms of innate host defense, of which antimicrobial peptides form a key part especially on epithelia and in neutrophil phagosomes. Here we demonstrate that the antimicrobial-peptide sensing system aps of the standard community-associated MRSA strain MW2 controls resistance to cationic antimicrobial peptides. The core of aps-controlled resistance mechanisms comprised the D-alanylation of teichoic acids (dlt operon), the incorporation of cationic lysyl-phosphatidylglycerol (L-PG) in the bacterial membrane (mprF), and the vraF/vraG putative antimicrobial peptide transporter. Further, the observed increased production of L-PG under the influence of cationic antimicrobial peptides was accompanied by the up-regulation of lysine biosynthesis. In noticeable difference to the aps system of S. epidermidis, only selected antimicrobial peptides strongly induced the aps response. Heterologous complementation with the S. epidermidis apsS gene indicated that this is likely caused by differences in the short extracellular loop of ApsS that interacts with the inducing antimicrobial peptide. Our study shows that the antimicrobial peptide sensor system aps is functional in the important human pathogen S. aureus, significant interspecies differences exist in the induction of the aps gene regulatory response, and aps inducibility is clearly distinguishable from effectiveness towards a given antimicrobial peptide. Keywords: Wild type control vs treated vs mutant Wild type untreated in triplicate is compared to wild type treated in triplicate along with three mutants in triplicate with and without treatment of indolicidin, totalling 30 samples

2008-04-06 | E-GEOD-8400 | biostudies-arrayexpress

The antimicrobial peptide-sensing system aps of Staphylococcus aureus

2008-04-07 | GSE8400 | GEO

Investigation into the effect of cathelicidin on autoimmune CD4+ T cells

Project description:We have shown that, in acute models of vaccination, the antimicrobial peptide cathelicidin potentiates Th17 cell differentiation. TO examine this in long-term, chronic inflammation, here we studied T cells in the mouse model of Multiple Sclerosis. We examined T cells from wildtype mice and those lacking cathelicidin.

2021-11-14 | GSE188655 | GEO

Homo sapiens

Project description:Human cathelicidin antimicrobial peptide LL37 effect on human neonatal epidermal keratinocytes (NHEKs).

| PRJNA213988 | ENA

Transcription profiling of human TLR2/1 stimulated human monocytes with the Mycobacterium tuberculosis derived 19kDa lipopeptide reveals Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

Project description:In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection. Experiment Overall Design: The monocyte microarrays were generated using primary human monocytes stimulated with a TLR2/1L or media at 0, 3, 6, 12, 24 hour timepoints. A total of 10 donors were used with time 0 h samples prepared for each. For time points, we used cells from 4 of the 10 donors to prepare media and TLR2/1-stimulated samples. Experiment Overall Design: Dendritic cells were generated by culturing primary human monocytes with GM-CSF (800 U/ml) and IL-4 (1000 U/ml) for 7 days. The cells were then harvested and recultured for 12 hours with TLR2/1L or media. A total of four donors were used. Experiment Overall Design: See manuscript for specific details on data analysis and experimental design and reagents.

2008-06-17 | E-GEOD-8921 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data