Dataset Information

Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-? Production by Epidermal Keratinocytes during Skin Injury.

ABSTRACT: Type 1 interferons (IFNs) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFN-? was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-? production depended on stimulation of mitochondrial antiviral-signaling protein (MAVS) by the antimicrobial peptide LL37 and double stranded-RNA released from necrotic cells. MAVS activated downstream TBK1 (TANK-Binding Kinase 1)-AKT (AKT serine/threonine kinase 1)-IRF3 (interferon regulatory factor 3) signaling cascade leading to IFN-? production and then promoted maturation of dendritic cells. In mice, the production of epidermal IFN-? by LL37 required MAVS, and human wounded and/or psoriatic skin showed activation of MAVS-associated IRF3 and induction of MAVS and IFN-? gene signatures. These findings show that KCs are an important source of IFN-? and MAVS is critical to this function, and demonstrates how the epidermis triggers unwanted skin inflammation under disease conditions.

SUBMITTER: Zhang LJ

PROVIDER: S-EPMC4957248 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury.

Zhang Ling-Juan LJ Sen George L GL Ward Nicole L NL Johnston Andrew A Chun Kimberly K Chen Yifang Y Adase Christopher C Sanford James A JA Gao Nina N Chensee Melanie M Sato Emi E Fritz Yi Y Baliwag Jaymie J Williams Michael R MR Hata Tissa T Gallo Richard L RL

Immunity 20160701 1

Type 1 interferons (IFNs) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFN-β was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-β production depended on stimulation of mitochondrial antiviral-signaling protein (MAVS) by the antimicrobial peptide LL37 and double stranded-RNA released from necrotic cells. MAVS activated downstream TBK1 (TANK-Binding Kinase 1)-AK ...[more]

PMID: 27438769

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Project description:BackgroundCathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications.MethodsSingleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48-72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed.ResultsCord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37.ConclusionCord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD.

Dataset Information

Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-? Production by Epidermal Keratinocytes during Skin Injury.

Publications

Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury.

Similar Datasets

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