Colonization and Infection of the Skin by <i>S. aureus</i> : Immune System Evasion and the Response to Cationic Antimicrobial Peptides

Ryu, Sunhyo,Song, Peter I.,Seo, Chang Ho,Cheong, Hyeonsook,Park, Yoonkyung Molecular Diversity Preservation International (MD 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.5

<P><I>Staphylococcus aureus</I> (<I>S. aureus</I>) is a widespread cutaneous pathogen responsible for the great majority of bacterial skin infections in humans. The incidence of skin infections by <I>S. aureus</I> reflects in part the competition between host cutaneous immune defenses and <I>S. aureus</I> virulence factors. As part of the innate immune system in the skin, cationic antimicrobial peptides (CAMPs) such as the β-defensins and cathelicidin contribute to host cutaneous defense, which prevents harmful microorganisms, like <I>S. aureus</I>, from crossing epithelial barriers. Conversely, <I>S. aureus</I> utilizes evasive mechanisms against host defenses to promote its colonization and infection of the skin. In this review, we focus on host-pathogen interactions during colonization and infection of the skin by <I>S. aureus</I> and methicillin-resistant <I>Staphylococcus aureus</I> (MRSA). We will discuss the peptides (defensins, cathelicidins, RNase7, dermcidin) and other mediators (toll-like receptor, IL-1 and IL-17) that comprise the host defense against <I>S. aureus</I> skin infection, as well as the various mechanisms by which <I>S. aureus</I> evades host defenses. It is anticipated that greater understanding of these mechanisms will enable development of more sustainable antimicrobial compounds and new therapeutic approaches to the treatment of <I>S. aureus</I> skin infection and colonization.</P>

우수 논문 소개 : 케라틴 세포에서 Malassezia furfur 감염에 대한 Cecropin A(1-8)-Magainin2(1-12) 하이브리드 펩타이드 유사체인 P5의 항생-항염 효과 규명

박윤경,( Peter I. Song ),김범준 생화학분자생물학회(구 한국생화학분자생물학회) 2012 생화학분자생물학회 소식 Vol.32 No.2

Scavenger Receptor Class A to E Involved in Various Cancers

류순효,Amanda Howland,Brendon Song,윤차경,Peter I Song 전남대학교 의과학연구소 2020 전남의대학술지 Vol.56 No.1

Scavenger receptors typically bind to multiple ligands on a cell surface, including endogenous and modified host-derived molecules and microbial pathogens. They promote the elimination of degraded or harmful substances such as non-self or altered-self targets through endocytosis, phagocytosis, and adhesion. Currently, scavenger receptors are subdivided into eight classes based on several variations in their sequences due to alternative splicing. Since recent studies indicate targeting scavenger receptors has been involved in cancer prognosis and carcinogenesis, we will focus on the current knowledge about the emerging role of scavenger receptor classes A to E in cancer progression.

Expression of Toll-Like Receptors in Verruca and Molluscum Contagiosum

Ja Kyung Ku,Peter I Song,Cheryl A. Armstrong,John C. Ansel,김형옥,Young Min Park,Hyun Jo Kwon,Mi Yeon Kim,Hoon Kang 대한의학회 2008 Journal of Korean medical science Vol.23 No.2

Recent studies indicate that several Toll-like receptors (TLRs) are implicated in recognizing viral structures and instigating immune responses against viral infections. The aim of this study is to examine the expression of TLRs and proinflammatory cytokines in viral skin diseases such as verruca vulgaris (VV) and molluscum contagiosum (MC). Reverse transcription-polymerase chain reaction and immunostaining of skin samples were performed to determine the expression of specific antiviral and proinflammatory cytokines as well as 5 TLRs (TLR2, 3, 4, 7, and 9). In normal human skin, TLR2, 4, and 7 mRNA was constitutively expressed, whereas little TLR3 and 9 mRNA was detected. Compared to normal skin (NS), TLR3 and 9 mRNA was clearly expressed in VV and MC specimens. Likewise, immunohistochemistry indicated that keratinocytes in NS constitutively expressed TLR2, 4, and 7; however, TLR3 was rarely detected and TLR9 was only weakly expressed, whereas 5 TLRs were all strongly expressed on the epidermal keratinocytes of VV and MC lesions. In addition, the mRNA expression of IFN- and TNF- was upregulated in the VV and MC samples. Immunohistochemistry indicated that IFN- and TNF- were predominately localized in the granular layer in the VV lesions and adjacent to the MC bodies. Our results indicated that VV and MC skin lesions expressed TLR3 and 9 in addition to IFN- and TNF- . These viral-induced proinflammatory cytokines may play a pivotal role in cutaneous innate immune responses.

Suppression of IRF4 by IRF1, 3, and 7 in Noxa expression is a necessary event for IFN-γ-mediated tumor elimination.

Piya, Sujan,Moon, Ae Ran,Song, Peter I,Hiscott, John,Lin, Rongtuan,Seol, Dai-Wu,Kim, Tae-Hyoung American Association for Cancer Research 2011 Molecular cancer research Vol.9 No.10

<P>IFN-gamma plays a critical role in tumor immunosurveillance by affecting either immune cells or tumor cells; however, IFN-mediated effects on tumor elimination are largely unknown. In this study, we showed that IFN regulatory factors (IRF) modulated by IFNs up- and downregulated Noxa expression, a prodeath BH3 protein, in various cancer cells. Inhibition of Noxa expression using short hairpin RNA in tumor cells leads to resistance against lipopolysaccharide (LPS)-induced tumor elimination, in which IFN-gamma is known as a critical effecter in mice. Chromatin immunoprecipitation analysis in both CT26 cells and SP2/0 cells, sensitive and resistant to LPS-induced tumor elimination, respectively, revealed that the responsiveness of IRF1, 3, 4, and 7 in the Noxa promoter region in response to IFN-gamma might be crucial in LPS-induced tumor elimination. IRF1, 3, and 7 were upregulated by IFN-gamma and activated Noxa expression, leading to the death of Noxa wild-type baby mouse kidney (BMK) cells but not of Noxa-deficient BMK cells. In contrast, IRF4 acts as a repressor for Noxa expression and inhibits cell death induced by IRF1, 3, or 7. Therefore, although IFN-gamma alone are not able to induce cell death in tumor cells in vitro, Noxa induction by IFN-gamma, which is regulated by the balance between its activators (IRF1, 3, and 7) and its repressor (IRF4), is crucial to increasing the susceptibility of tumor cells to immune cell-mediated cytotoxicity. Mol Cancer Res; 9(10); 1356-65. (C) 2011 AACR.</P>

Melanoma Cell Death Mechanisms

Lindsey Broussard,Amanda Howland,류순효,Kyungsup Song,David Norris,Cheryl A. Armstrong,Peter I Song 전남대학교 의과학연구소 2018 전남의대학술지 Vol.54 No.3

Over recent years, several new molecular and immunogenic therapeutic approaches to melanoma treatment have been approved and implemented in clinical practice. Mechanisms of resistance to these new therapies have become a major problem. Mutation-specific pharmacotherapy can result in simultaneous emergence of resistant clones at many separate body sites despite an initially positive therapeutic response. Additionally, treatments aimed at inducing apoptosis are subject to resistance due to escape through other known mechanisms of regulated cell death (RCD). In this review, we discuss the complexity in pharmacological manipulation of melanoma with c-Kit, BRAF, MEK, and/or mTOR mutant cell lines. This study also addresses melanoma evasion of cell death through modalities of RCD such as apoptosis, autophagy, and necroptosis. This study also examines new combination therapies which have been approved to target both cell cycle dysregulation and cell death pathways. Lastly, we recognize the importance of immunomodulation though manipulation of the body’s natural killing mechanisms with CTLA4, PD1, and CSF1 inhibition. As we begin to recognize tumor cell activation of alternate pathways, evasion of programmed cell death, and manipulation of the tumor microenvironment, it is increasingly important to grasp the complexity of personalized therapy in melanoma treatment.

Therapeutic Effects of Synthetic Antimicrobial Peptides, TRAIL and NRP1 Blocking Peptides in Psoriatic Keratinocytes

류순효,Lindsey Broussard,윤차경,Brendon Song,David Norris,Cheryl A. Armstrong,Beom Joon Kim,Peter I Song 전남대학교 의과학연구소 2019 전남의대학술지 Vol.55 No.2

Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States. Currently, several biologic agents that target different molecules implicated in the pathogenic processes of psoriasis are being assessed in diverse clinical studies. However, relapse usually occurs within weeks or months, meaning there is currently no cure for psoriasis. Therefore, recent studies have discovered diverse new potential treatments for psoriasis: inhibitors of bacteria such as Staphylococcus aureus, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and neuropilin 1 (NRP1). A promising approach that has recently been described involves modifying antimicrobial peptides to develop new cutaneous anti-bacterial agents that target inflammatory skin disease induced by Staphylococcus. Increased expression of TRAIL and its death receptors DR4 and DR5 has been implicated in the pathogenesis of plaque psoriasis. In addition, TRAIL has the ability to inhibit angiogenesis by inducing endothelial cell death and by negative regulation of VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Since NRP1 regulates angiogenesis induced by multiple signals, including VEGF, ECM and semaphorins, and also initiates proliferation of keratinocytes through NF-kB signaling pathway in involved psoriatic skin, targeting NRP1 pathways may offer numerous windows for intervention in psoriasis. In this review, we will focus on the current knowledge about the emerging role of synthetic antimicrobial peptides, TRAIL and NRP1 blocking peptides in the pathogenesis and treatment of psoriasis.

Therapeutic Inhibitors against Mutated BRAF and MEK for the Treatment of Metastatic Melanoma

류순효,윤차경,문애란,Amanda Howland,Cheryl A. Armstrong,Peter I Song 전남대학교 의과학연구소 2017 전남의대학술지 Vol.53 No.3

Melanoma is one of the most aggressive cancers in the world and is responsible for the majority of skin cancer deaths. Recent advances in the field of immunotherapy using active, adoptive, and antigen-specific therapeutic approaches, have generated the expectation that these technologies have the potential to improve the treatment of advanced malignancies, including melanoma. Treatment options for metastatic melanoma patients have been dramatically improved by the FDA approval of new therapeutic agents including vemurafenib, dabrafenib, and sorafenib. These kinase inhibitors have the potential to work in tandem with MEK, PI3K/AKT, and mTOR to inhibit the activity of melanoma inducing BRAF mutations. This review summarizes the effects of the new therapeutic agents against melanoma and the underlying biology of these BRAF inhibitors.

Immunohistochemical detection of StarD6 in the rat nervous system

Chang, In-Youb,Kim, Jin Ho,Hwang, Gul,Song, Peter I.,Song, Rack Jong,Kim, Jung Woo,Yoon, Sang Pil Lippincott Williams Wilkins, Inc. 2007 NEUROREPORT - Vol.18 No.15

Steroidogenic acute regulatory (StAR)-related lipid transfer (START) domain 6 (StarD6) is known to be exclusively expressed in germ cells of testis. As little is known about StarD6 expression in the nervous system, we investigated the distribution of StarD6 in rat neural tissues. Immunoreactivity of StarD6 was detected in the brain, spinal cord and dorsal root ganglia; particularly cerebral cortex (layer V and VI), hippocampus, substantia gelatinosa of the spinal cord. We provided compelling evidence that multiple neuronal and glial populations were immunolabelled with anti-StarD6 antibody throughout the nervous system. We postulate that StarD6 might play an important role in lipid sensing of the nervous system based on its immunolocalization in this study.

Expression of Toll-Like Receptors in Verruca and Molluscum Contagiosum

Ku, Ja Kyung,Kwon, Hyun Jo,Kim, Mi-Yeon,Kang, Hoon,Song, Peter I,Armstrong, Cheryl A.,Ansel, John C.,Kim, Hyung Ok,Park, Young Min The Korean Academy of Medical Sciences 2008 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.23 No.2

<P>Recent studies indicate that several Toll-like receptors (TLRs) are implicated in recognizing viral structures and instigating immune responses against viral infections. The aim of this study is to examine the expression of TLRs and proinflammatory cytokines in viral skin diseases such as verruca vulgaris (VV) and molluscum contagiosum (MC). Reverse transcription-polymerase chain reaction and immunostaining of skin samples were performed to determine the expression of specific antiviral and proinflammatory cytokines as well as 5 TLRs (TLR2, 3, 4, 7, and 9). In normal human skin, TLR2, 4, and 7 mRNA was constitutively expressed, whereas little TLR3 and 9 mRNA was detected. Compared to normal skin (NS), TLR3 and 9 mRNA was clearly expressed in VV and MC specimens. Likewise, immunohistochemistry indicated that keratinocytes in NS constitutively expressed TLR2, 4, and 7; however, TLR3 was rarely detected and TLR9 was only weakly expressed, whereas 5 TLRs were all strongly expressed on the epidermal keratinocytes of VV and MC lesions. In addition, the mRNA expression of IFN-β and TNF-α was upregulated in the VV and MC samples. Immunohistochemistry indicated that IFN-β and TNF-α were predominately localized in the granular layer in the VV lesions and adjacent to the MC bodies. Our results indicated that VV and MC skin lesions expressed TLR3 and 9 in addition to IFN-β and TNF-α. These viral-induced proinflammatory cytokines may play a pivotal role in cutaneous innate immune responses.</P>