Interleukin-36 (IL-36) family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to... more
Interleukin-36 (IL-36) family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to promote wound healing remains unknown. Here we demonstrated that skin injury increased the expression of IL-36γ to promote wound healing. Mechanistically, the expression of IL-36γ was induced by RNAs from damaged cells via the activation of Toll-like receptor 3 (TLR3) and TIR-domain-containing adapter-inducing interferon-β (TRIF) followed by the induction of a zinc finger protein SLUG to abrogate the inhibitory effect of vitamin D receptor (VDR) on the promoter of IL-36γ gene. IL-36γ acted back on keratinocytes to induce regenerating islet-derived protein 3-alpha (REG3A), which regulated keratinocyte proliferation and differentiation, thus promoting wound re-epithelialization. These observations demonstrate that skin injury increases IL-36γ via the acti...
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Psoriasis is a chronic autoinflammatory skin disease. Although interleukin-17, derived from lymphocytes, has been shown to be critical in psoriasis, the initiation and maintenance of chronic skin inflammation has not been well understood.... more
Psoriasis is a chronic autoinflammatory skin disease. Although interleukin-17, derived from lymphocytes, has been shown to be critical in psoriasis, the initiation and maintenance of chronic skin inflammation has not been well understood. IL-25 (also called IL-17E), another IL-17 family cytokine, is well known to regulate allergic responses and type 2 immunity. Here we have shown that IL-25, also highly expressed in the lesional skin of psoriasis patients, was regulated by IL-17 in murine skin of a imiquimod (IMQ)-induced psoriasis model. IL-25 injection induced skin inflammation, whereas germline or keratinocyte-specific deletion of IL-25 caused resistance to IMQ-induced psoriasis. Via IL-17RB expression in keratinocytes, IL-25 stimulated the proliferation of keratinocytes and induced the production of inflammatory cytokines and chemokines, via activation of the STAT3 transcription factor. Thus, our data demonstrate that an IL-17-induced autoregulatory circuit in keratinocytes is m...
Research Interests: Immunology, Biology, Inflammation, Medicine, Immunity, and 5 morePsoriasis, Cytokine, Chemokine, Keratinocyte, and Imiquimod
NF-κB is constitutively activated in psoriatic epidermis. However, how activated NF-κB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-κB activation triggered by inflammatory cytokines... more
NF-κB is constitutively activated in psoriatic epidermis. However, how activated NF-κB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-κB activation triggered by inflammatory cytokines induces the transcription of microRNA (miRNA) miR-31, one of the most dynamic miRNAs identified in the skin of psoriatic patients and mouse models. The genetic deficiency of miR-31 in keratinocytes inhibits their hyperproliferation, decreases acanthosis and reduces the disease severity in psoriasis mouse models. Furthermore, protein phosphatase 6 (ppp6c), a negative regulator that restricts the G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. The inhibition of ppp6c is functionally important for miR-31-mediated biological effects. Moreover, NF-κB activation inhibits ppp6c expression directly through the induction of miR-31, and enhances keratinocyte proliferation. Thus, our data identify NF-κB...
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Book Description: The human skin is constantly exposed to a large number of external pathogens, due to daily contact with the environment. The observation that extensive skin infections are relatively rare suggests the presence of an... more
Book Description: The human skin is constantly exposed to a large number of external pathogens, due to daily contact with the environment. The observation that extensive skin infections are relatively rare suggests the presence of an efficient host defense system at the skin surface. Recent findings indicate the importance of keratinocytes as effectors of innate immunity, but also as regulators of acquired immune responses, inflammation and wound repair. This book considers the current findings regarding the role of keratinocytes in the epidermis with special interest to mechanisms involved in host defense. Finally, the clinical relevance of the functions of keratinocytes in the innate immunity is also discussed. (Imprint: Nova Biomedical) Table of Contents: Preface Chapter 1. Dynamic Interplay between Cell Types during Wound Healing (Simona Martinotti and Elia Ranzato, DiSIT - Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, It...
Antimicrobial peptides from human skin are an important component of the innate immune response and play a key role as a first line of defense against infections. One such peptide is the recently discovered dermcidin-1L. To better... more
Antimicrobial peptides from human skin are an important component of the innate immune response and play a key role as a first line of defense against infections. One such peptide is the recently discovered dermcidin-1L. To better understand its mechanism and to further investigate its antimicrobial spectrum, recombinant dermcidin-1L was expressed in Escherichia coli as a fusion protein and purified
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Research Interests: Cytokines, Innate immunity, Signal Transduction, Toll like receptor signaling, Toll Like Receptors, and 14 moreAssociation study, Cell line, Humans, Child, Developing Country, Mice, Animals, Gene Polymorphism, Tumor necrosis factor-alpha, Otitis Media, Murine Model, Bacterial Infection, Haemophilus Infections Market, and Haemophilus influenzae
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Research Interests:
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Research Interests: Drug development, Multidisciplinary, Signal Transduction, Humans, Protein Kinases, and 14 moreGram Positive, Human Body, Phenotype, Antimicrobial Peptide, Staphylococcus epidermidis, Gram Positive Bacteria, Gram-negative bacteria, High Density Concrete, Beta Defensins, Amino Acid Sequence, Sensor system, Sensitivity and Specificity, Resistance Genes Mechanism), and Host Defense
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Research Interests: Engineering, Physics, Chemistry, Biology, Immunohistochemistry, and 20 moreMedicine, Multidisciplinary, Humans, Lipid Membranes, Bacterial Toxins, Mice, Animals, Antimicrobial activity, Streptococcus Pyogenes, Peptides, Skin, Immunoprecipitation, Antimicrobial Peptide, PLoS one, Staphylococcus epidermidis, Neutrophils, Spectrum analysis, Protein Binding, Innate Immune System, and Host Defense
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Research Interests: Microbiology, Molecular Microbiology, Biological Sciences, Molecular, Bacteria, and 10 moreStaphylococcus aureus, Mechanism, Peptides, Antimicrobial Peptide, Staphylococcus epidermidis, Anti-Bacterial Agents, Microbial Sensitivity Tests, Microbial Viability, Gene Expression Regulation, and Gene expression profiling
Research Interests: Gene Silencing, Signal Transduction, Toll like receptor signaling, Humans, Keratinocytes, and 13 moreMice, Animals, Staphylococcus aureus, Streptococcus Pyogenes, Sterilization, Epidermis, Antimicrobial Peptide, Staphylococcus epidermidis, Clinical Sciences, mRna expression levels, Beta Defensins, INVESTIGATIVE, and Neutralizing antibodies
Research Interests: Symbiosis, Innate immunity, Humans, Keratinocytes, Circular Dichroism, and 14 moreLipid Membranes, Bacterial Toxins, Mice, Animals, Staphylococcus aureus, Streptococcus Pyogenes, Epidermis, Antimicrobial Peptide, Staphylococcus epidermidis, Clinical Sciences, Antimicrobial Cationic Peptides, Protein Secondary Structure Prediction, Lipid bilayers, and INVESTIGATIVE
Staphylococci are important opportunistic pathogens. However, there is a lack of information on how these bacteria survive inside the human body during infection. This study demonstrates that quorum-sensing regulation in Staphylococcus... more
Staphylococci are important opportunistic pathogens. However, there is a lack of information on how these bacteria survive inside the human body during infection. This study demonstrates that quorum-sensing regulation in Staphylococcus epidermidis protects it from key mechanisms of human innate host defense. To gain a better understanding of the basis of the observed phenotype, the agr quorum-sensing regulon of S.