Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium

Zhang, Mi; Lü, Xiaoli; Jeffrey, C.; Ng, Bobby G.; Wang, Guiqiang; Lechman, Eric R.; Watkins, Simon C.; Rabinowich, Hannah; Robbins, Paul D.

doi:10.1016/s1525-0016(03)00181-3

Cited by 66 publications

(52 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So far, there have been several reports of CPP conjugates that can attenuate inflammatory-disease-associated responses, particularly in models of rheumatoid arthritis. One example of this is an apoptosis-inducing fusion protein that reduces synovial inflammation when administered to rabbit joints (Mi et al, 2003). Another example is a fusion protein derived from the NEMObinding domain (NBD) and the PTD of Tat, which was used to block nuclear factor-B activation, with consequent reduced cytokine production and inhibition of joint inflammation (May et al, 2000;Dai et al, 2004;Jimi et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines

Rüter

Buss

Scharnert

et al. 2010

Journal of Cell Science

View full text Add to dashboard Cite

SummaryCell-permeable proteins, also called cell-penetrating peptides (CPPs), have the ability to cross cellular membranes, either alone or in association with bioactive cargo. We identified the Yersinia protein YopM as a novel bacterial cell-permeable protein. Here, we describe the ability of isolated recombinant YopM to enter host cells without a requirement for additional factors. This autonomous translocation of YopM was confirmed in several cell types, indicating that it is an intrinsic property of YopM. Using truncated versions of YopM, we show that either of the two N-terminal -helices of YopM mediates translocation into the cells. Furthermore, the two -helices are also able to deliver heterologous cargo, such as GFP or YopE. In addition, we found that, after entering the cells, YopM is functional and efficiently downregulates the transcription of pro-inflammatory cytokines (such as tumor necrosis factor- and interleukins 12, 15 and 18). This finding suggests the potential use of YopM as a tool for protein delivery. Furthermore, it can lead to important advances in understanding and evaluating the intracellular and molecular function of YopM without the need for infection with Yersinia.

show abstract

Section: Discussionmentioning

confidence: 99%

A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines

Rüter

Buss

Scharnert

et al. 2010

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Recently, one PTD was shown to specifically transduce synovial fibroblasts and was able to cause specific cell death by delivering apoptotic agents exclusively to these cells [126], demonstrating that cell specificity can occur for some CPPs, although the mechanism behind this remains a mystery.…”

Section: Dna Compaction/protectionmentioning

confidence: 99%

Protein Transduction: Cell Penetrating Peptides and Their Therapeutic Applications

Wagstaff¹,

Jans

2006

CMC

160

View full text Add to dashboard Cite

Cell penetrating proteins or peptides (CPPs) have the ability to cross the plasma membranes of mammalian cells in an apparently energy- and receptor-independent fashion. Although there is much debate over the mechanism by which this "protein transduction" occurs, the ability of CPPs to translocate rapidly into cells is being exploited to deliver a broad range of therapeutics including proteins, DNA, antibodies, oligonucleotides, imaging agents and liposomes in a variety of situations and biological systems. The current review looks at the delivery of many such molecules by various CPPs, and their potential therapeutic application in a wide range of areas. CPP ability to deliver different cargoes in a relatively efficient and non-invasive manner has implications as far reaching as drug delivery, gene transfer, DNA vaccination and beyond. Although many questions remain to be answered and limitations on the use of CPPs exist, it is clear that this emerging technology has much to offer in a clinical setting.

show abstract

“…The first protein reported with transductional properties was the HIV transactivator protein TAT, in which the 11-aa PTD was identified by virtue of its cationic content (9). Recently, PTDs have been characterized that mediate efficient and rapid receptor-independent internalization of peptide-protein conjugates (10). These cationic transduction peptides transduce a wide variety of cells similar to the HIV TAT, mediating highly efficient transduction in vitro and in vivo (11,12).…”

mentioning

confidence: 99%

Amelioration of Chronic Murine Colitis by Peptide-Mediated Transduction of the IκB Kinase Inhibitor NEMO Binding Domain Peptide

Davé¹,

Tilstra²,

Matsuoka³

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

The NF-κB family of transcription factors is a central regulator of chronic inflammation. The phosphorylation of IκB proteins by the IκB kinase (IKK) complex (IKKα, IKKβ, and NF-κB essential modulator or NEMO) is a key step in NF-κB activation. Peptides corresponding to the NEMO binding domain (NBD) of IKK blocks NF-κB activation without inhibiting basal NF-κB activity. In this report, we determined the effects of the IKK inhibitor peptide (NBD) in a model of spontaneously occurring chronic murine colitis, the IL-10-deficient (IL-10−/−) mouse. Using a novel cationic peptide transduction domain (PTD) consisting of eight lysine residues (8K), we were able to transduce the NBD peptide into cells and tissues. In a NF-κB reporter system, 8K-NBD dose-dependently inhibits TNF-induced NF-κB activation. Furthermore, 8K-NBD inhibited nuclear translocation of NF-κB family members. In NF-κBEGFP knock-in mice, 8K-NBD inhibited LPS-activated NF-κB (EGFP activity) in the ileum but did not inhibit basal NF-κB in Peyer’s patches. IL-10−/− mice treated systemically with 8K-NBD demonstrate amelioration of established colitis, decreased NF-κB activation in the lamina propria, and a reduction in spontaneous intestinal IL-12 p40, TNF, IFN-γ, and IL-17 production. These results demonstrate that inhibitors of IKK, in particular a PTD-NBD peptide, may be therapeutic in the treatment of inflammatory bowel disease.

show abstract

Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium

Cited by 66 publications

References 35 publications

A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines

A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines

Protein Transduction: Cell Penetrating Peptides and Their Therapeutic Applications

Amelioration of Chronic Murine Colitis by Peptide-Mediated Transduction of the IκB Kinase Inhibitor NEMO Binding Domain Peptide

Contact Info

Product

Resources

About