Project description:Gene expression in THP-1 cells treated for 6 hours with CNT and GNP conjugated with LL-37, LL-37 spiked as well as free LL-37: Reference (Total RNA Mixture of all samples) vs. treated cells
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.
Project description:Clostridium difficile is a major nosocomial pathogen that causes severe diarrheal disease. Though C. difficile is known to inhabit the human gastrointestinal tract, the mechanisms that allow this pathogen to adapt to the intestine and survive host defenses are not known. In this work, we investigated the response of C. difficile to the host defense peptide, LL-37, to determine the mechanisms underlying host adaptation and survival. Expression analyses revealed a previously unknown locus, which we named clnRAB, that is highly induced by LL-37 and acts as a global regulator of gene expression in C. difficile. Mutant analyses indicate that ClnRAB is a novel regulatory system that senses LL-37 as a host signal to regulate adaptation to the intestinal environment.
