The expression of legumain, an asparaginyl endopeptidase that controls antigen processing, is reduced in endotoxin-tolerant monocytes

Wolk, Kerstin; Grütz, Gerald; Witte, Katrin; Volk, Hans‐Dieter; Sabat, Robert

doi:10.1038/sj.gene.6364224

Cited by 49 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Legumain encodes another cysteine protease that is localized to the lysosomal/endosomal system and functions in antigen presentation. Legumain is also overexpressed in diverse tumors and linked to invasion and migration in vitro [252, 253]. …”

Section: Hmga1 Transcriptional Targetsmentioning

confidence: 99%

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

Sumter¹,

Xian²,

Huso³

et al. 2016

CMM

103

View full text Add to dashboard Cite

Background & Objectives Chromatin structure is the single most important feature that distinguishes a cancer cell from a normal cell histologically. Chromatin remodeling proteins regulate chromatin structure and high mobility group A (HMGA1) proteins are among the most abundant, nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells, while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1 “transcriptome” is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss studies linking HMGA1 to Alzheimer’s disease and type-2 diabetes. Conclusion Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.

show abstract

Section: Hmga1 Transcriptional Targetsmentioning

confidence: 99%

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

Sumter¹,

Xian²,

Huso³

et al. 2016

CMM

103

View full text Add to dashboard Cite

show abstract

“…Isolation of total cellular RNA from mouse tissue and human cells was performed using Invisorb RNA kit II (Invitek). The mRNA was reverse transcribed as described previously [34,38]. Quantitative PCR analyses were done using the ABI Prism 7700 Sequence Detection System (Applied Biosystems, Weiterstadt, Germany).…”

Section: Quantitative Mrna Analysismentioning

confidence: 99%

Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes

Wolk

Witte

et al. 2008

Journal of Leukocyte Biology

145

110

View full text Add to dashboard Cite

IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29 are new members of the IL-10 interferon family. Monocytes are well-known sources of IL-19, IL-20, and IL-24. We demonstrated here that monocytes also expressed IL-29, and monocyte differentiation into macrophages (Mphi) or dendritic cells (DCs) strongly changed their production capacity of these cytokines. Maturation of DCs with bacterial stimuli induced high expression of IL-28/IL-29 and IL-20. Simulated T cell interaction and inflammatory cytokines induced IL-29 and IL-20 in maturing DCs, respectively. Compared with monocytes, DCs expressed only minimal IL-19 levels and no IL-24. The differentiation of monocytes into Mphi reduced their IL-19 and terminated their IL-20, IL-24, and IL-29 production capacity. Like monocytes, neither Mphi nor DCs expressed IL-22 or IL-26. The importance of maturing DCs as a source of IL-28/IL-29 was supported by the much higher mRNA levels of these mediators in maturing DCs compared with those in CMV-infected fibroblasts, and the presence of IL-28 in lymph nodes but not in liver of lipopolysaccharide-injected mice. IL-19, IL-20, IL-22, IL-24, and IL-26 do not seem to affect Mphi or DCs as deduced from the lack of corresponding receptor chains. The significance of IL-20 and IL-28/IL-29 coexpression in maturing DCs may lie in the broadly amplified innate immunity in neighboring tissue cells like keratinocytes. In fact, IL-20 induced the expression of antimicrobial proteins, whereas IL-28/IL-29 enhanced the expression of toll-like receptors (TLRs) and the response to TLR ligands. However, the strongest response to TLR2 and TLR3 activation showed keratinocytes in the simultaneous presence of IL-20 and IL-29.

show abstract

“…Messenger RNA was reversetranscribed and quantitative PCR analysis was performed in triplicate assays using the ABI Prism 7700 Sequence Detection System (Applied Biosystems) as described previously. 51,52 For the detection of total IFN-lR1 and single splice variants, systems purchased from Applied Biosystems, together with the matching system for the housekeeping gene hypoxanthine phosphoribosyl-transferase 1 (HPRT), were used. The analysis of HPRT was included to normalize IFN-lR1 expression, which was carried out by calculating IFNlR1 expression as the value 2 to the power of the difference between the threshold cycles for amplification of HPRT and IFN-lR1.…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

Despite IFN-λ receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines

et al. 2009

Self Cite

View full text Add to dashboard Cite

Interferon (IFN)-l1, -2 and -3 (also designated as interleukin (IL)-29, IL-28a and IL-28b) represent a new subfamily within the class II cytokine family. They show type I IFN-like antiviral and cytostatic activities in affected cells forming the basis for IFN-l1 therapy currently under development for hepatitis C infection. However, many aspects of IFN-ls are still unknown. This study aimed at identifying the target cells of IFN-ls within the immune system and the skin. Among skin cell populations, keratinocytes and melanocytes, but not fibroblasts, endothelial cells or subcutaneous adipocytes turned out to be targets. In contrast to these target cells, blood immune cell populations did not clearly respond to even high concentrations of these cytokines, despite an IFN-l receptor expression. Interestingly, immune cells expressed high levels of a short IFN-l receptor splice variant (sIFN-lR1/sIL-28R1). Its characterization revealed a secreted, glycosylated protein that binds IFN-l1 with a moderate affinity (K D 73 nM) and was able to inhibit IFN-l1 effects. Our study suggests that IFN-l therapy should be suited for patients with verrucae, melanomas and non-melanoma skin cancers, apart from patients with viral hepatitis, and would not be accompanied by immune-mediated complications known from type I IFN application.

show abstract

The expression of legumain, an asparaginyl endopeptidase that controls antigen processing, is reduced in endotoxin-tolerant monocytes

Cited by 49 publications

References 36 publications

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes

Despite IFN-λ receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines

Contact Info

Product

Resources

About