Purification and Characterization of Human Neutrophil Peptide 4, a Novel Member of the Defensin Family

Wilde, Craig G.; Griffith, J E; Marra, MN; Snable, J L; Scott, RW

doi:10.1016/s0021-9258(18)60449-1

Cited by 201 publications

(39 citation statements)

References 22 publications

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“…Among these genes, the highest-scoring node, also known as the seed node, was defensin alpha 4 (DEFA4; mean log 2 FC = 2.88 and total degree = 14) and the gene with the highest log 2 FC value was olfactomedin 4 (OLFM4; mean log 2 FC = 3.82 and total degree = 10). DEFA4 encodes a member of defensins thought to be associated with host defense and OLFM4 encodes an anti-apoptotic factor that promotes tumor growth [33,34]. Since the 2 genes were reported as up-regulated DEGs of sJIA by Brachat et al, we were able to confirm that our result conformed with the previous research [11].…”

Section: Identification Of Key Genes Among the Sjia Signature By Network Analysissupporting

confidence: 89%

“…Up-regulated genes of the sJIA signature were enriched in innate immune processes and pathways related to producing red blood cells (Figure 3A). Among the 103 up-regulated genes, the most significant gene cluster was detected by PPI network analysis and the seed node of the cluster was DEFA4, which encodes a member of the defensin family of antimicrobial and cytotoxic peptides involved in host defense (Figure 4A) [33]. Based on the GO database, each gene of the cluster, including DEFA4, was identified as involved in neutrophil degranulation associated with innate immune processes [27,62].…”

Section: Discussionmentioning

confidence: 99%

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An Integrative Transcriptomic Analysis of Systemic Juvenile Idiopathic Arthritis for Identifying Potential Genetic Markers and Drug Candidates

Kim

Song

Lee

et al. 2021

IJMS

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Systemic juvenile idiopathic arthritis (sJIA) is a rare subtype of juvenile idiopathic arthritis, whose clinical features are systemic fever and rash accompanied by painful joints and inflammation. Even though sJIA has been reported to be an autoinflammatory disorder, its exact pathogenesis remains unclear. In this study, we integrated a meta-analysis with a weighted gene co-expression network analysis (WGCNA) using 5 microarray datasets and an RNA sequencing dataset to understand the interconnection of susceptibility genes for sJIA. Using the integrative analysis, we identified a robust sJIA signature that consisted of 2 co-expressed gene sets comprising 103 up-regulated genes and 25 down-regulated genes in sJIA patients compared with healthy controls. Among the 128 sJIA signature genes, we identified an up-regulated cluster of 11 genes and a down-regulated cluster of 4 genes, which may play key roles in the pathogenesis of sJIA. We then detected 10 bioactive molecules targeting the significant gene clusters as potential novel drug candidates for sJIA using an in silico drug repositioning analysis. These findings suggest that the gene clusters may be potential genetic markers of sJIA and 10 drug candidates can contribute to the development of new therapeutic options for sJIA.

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Section: Identification Of Key Genes Among the Sjia Signature By Network Analysissupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

An Integrative Transcriptomic Analysis of Systemic Juvenile Idiopathic Arthritis for Identifying Potential Genetic Markers and Drug Candidates

Kim

Song

Lee

et al. 2021

IJMS

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“…Because of the high sequence similarity and difficulties in purifying the individual peptides as well as the high degree in functional similarity, the HNP1-3 are often studied as a group, although certain studies have demonstrated differences in their antimicrobial (Lehrer et al 1988) and immunomodulatory activities (Chertov et al 1996). HNP4 was identified as a HNP due to its structural homology to the HNP1-3 (Wilde et al 1989). This gene differs from the other genes of this family by an extra 83-base pair segment that is apparently the result of a recent duplication within the coding region (Palfree et al 1993).…”

Section: Host Defence Peptides In Humansmentioning

confidence: 99%

“…As with the other HNPs, HNP4 is found in the neutrophils, but is also called corticostatin because it exhibits corticostatic activity and inhibits corticotrophin-stimulated corticosterone production (Singh et al 1988). Despite its variation from the conserved sequences of HNP1-3, it appears to have much more potent antimicrobial activity (Wilde et al 1989).…”

Section: Host Defence Peptides In Humansmentioning

confidence: 99%

Immunomodulatory Properties of Defensins and Cathelicidins

Bowdish

Davidson

Hancock

2006

Current Topics in Microbiology and Immunology

194

186

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Host defence peptides are a conserved component of the innate immune response in all complex life forms. In humans, the major classes of host defence peptides include the αand β-defensins and the cathelicidin, hCAP-18/LL-37. These peptides are expressed in the granules of neutrophils and by a wide variety of tissue types. They have many roles in the immune response including both indirect and direct antimicrobial activity, the ability to act as chemokines as well as induce chemokine production leading to recruitment of leukocytes to the site of infection, the promotion of wound healing and an ability to modulate adaptive immunity.

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“…Several rabbit α-defensins have been identified, including NP-1 and NP-2, the two most cationic peptides with a broad spectrum of activity against both Gram-positive and -negative bacteria [ 317 ]. Human α-defensins HNP1–4 are secreted by neutrophils [ 318 , 319 ], whereas HD-5 and HD-6 are secreted by Paneth cells located in the intestinal epithelium [ 320 , 321 , 322 ]. HNP1 is the most well-studied α-defensin with activity against S. aureus , B. subtilis , S. epidermis , and E. coli [ 323 ] resulting from the inhibition of DNA and protein synthesis [ 324 ].…”

Section: Sources Of Ampsmentioning

confidence: 99%

Antimicrobial Peptides: An Update on Classifications and Databases

Hafeez

Jiang

Bergen

et al. 2021

IJMS

155

142

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Antimicrobial peptides (AMPs) are distributed across all kingdoms of life and are an indispensable component of host defenses. They consist of predominantly short cationic peptides with a wide variety of structures and targets. Given the ever-emerging resistance of various pathogens to existing antimicrobial therapies, AMPs have recently attracted extensive interest as potential therapeutic agents. As the discovery of new AMPs has increased, many databases specializing in AMPs have been developed to collect both fundamental and pharmacological information. In this review, we summarize the sources, structures, modes of action, and classifications of AMPs. Additionally, we examine current AMP databases, compare valuable computational tools used to predict antimicrobial activity and mechanisms of action, and highlight new machine learning approaches that can be employed to improve AMP activity to combat global antimicrobial resistance.

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Purification and Characterization of Human Neutrophil Peptide 4, a Novel Member of the Defensin Family

Cited by 201 publications

References 22 publications

An Integrative Transcriptomic Analysis of Systemic Juvenile Idiopathic Arthritis for Identifying Potential Genetic Markers and Drug Candidates

An Integrative Transcriptomic Analysis of Systemic Juvenile Idiopathic Arthritis for Identifying Potential Genetic Markers and Drug Candidates

Immunomodulatory Properties of Defensins and Cathelicidins

Antimicrobial Peptides: An Update on Classifications and Databases

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