Gene induction during differentiation of human monocytes into dendritic cells: an integrated study at the RNA and protein levels

Angénieux, Catherine; Fricker, Dominique; Strub, Jean‐Marc; Luche, Sylvie; Bausinger, Huguette; Cazenave, Jean‐Pierre; Dorsselaer, Alain Van; Hanau, Daniel; Salle, Henri; Rabilloud, Thierry

doi:10.1007/s101420100037

Cited by 22 publications

(26 citation statements)

References 27 publications

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“…While the relative gene expression of the cytosolic enzymes Catalase and CuZnSOD revealed a significant increase in DC compared to monocytes (12.7 and 6 fold, respectively), no induction was observed in the RNA level of MnSOD (0.21 fold). This apparently contrasting observation that a major induction of MnSOD is seen at the protein level than at the RNA level has been also reported previously (Angenieux et al, 2001) and explained considering that the localization into the mitochondrial matrix would protect the mature mitochondrial protein from proteolytic degradation. Consequently, it can be deduced that during DC differentiation process, taking place in 6-days culture, large increase in the concentration of mitochondrial proteins, such as MnSOD, can occur from marginal increase of the corresponding mRNA levels (Angenieux et al, 2001).…”

Section: Resultssupporting

confidence: 45%

“…This apparently contrasting observation that a major induction of MnSOD is seen at the protein level than at the RNA level has been also reported previously (Angenieux et al, 2001) and explained considering that the localization into the mitochondrial matrix would protect the mature mitochondrial protein from proteolytic degradation. Consequently, it can be deduced that during DC differentiation process, taking place in 6-days culture, large increase in the concentration of mitochondrial proteins, such as MnSOD, can occur from marginal increase of the corresponding mRNA levels (Angenieux et al, 2001). Overall, these findings confirmed previous observations (Rivollier et al, 2006) showing that DC are equipped with a very efficient anti-oxidant systems that may assure higher resistance to oxidative environments.…”

Section: Resultssupporting

confidence: 45%

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An active mitochondrial biogenesis occurs during dendritic cell differentiation

Zaccagnino

Saltarella

Maiorano

et al. 2012

The International Journal of Biochemistry & Cell Biology

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. b s t r a c tDendritic cells (DC) are sentinels of the immune system deriving from circulating monocyte precursors recruited to sites of inflammation. In a previous report (Del Prete et al., 2008) we showed that, after differentiation, DC exhibited increased number of condensed mitochondria and dynamic changes in their energy metabolism. A study is presented here showing that the DC differentiation process is characterized by increased expression level and activity of mitochondrial respiratory complexes, as well as by an increased mitochondrial DNA (mtDNA) copy number. Moreover, DC are equipped with more efficient antioxidant protection systems, over expressed most likely to detoxify increased ROS production, as a consequence of the much higher mitochondrial activity. Kinetic analysis of the three main mitochondrial biogenesis-associated genes revealed that the peak in PPAR␥ coactivator-1alpha (PGC-1␣) gene expression was suddenly reached few hours after the onset of the differentiation. While PGC-1␣ expression rapidly declines, the mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) expression gradually increased. These findings demonstrate that an active mitochondrial biogenesis occurs during DC differentiation and further suggest that an early input by the master regulator of mitochondrial biogenesis PGC-1␣ is needed to trigger the subsequent activation of the downstream transcription factors, NRF-1 and TFAM in this process.

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Section: Resultssupporting

confidence: 45%

Section: Resultssupporting

confidence: 45%

An active mitochondrial biogenesis occurs during dendritic cell differentiation

Zaccagnino

Saltarella

Maiorano

et al. 2012

The International Journal of Biochemistry & Cell Biology

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“…There are indications that other important physiological and pathological processes, such as cell differentiation (Angenieux et al, 2001), immortalization (Kim et al, 2001) or tumorigenesis (Ojala et al, 2002;Haugen et al, 2003;Baris et al, 2004), are also associated with alterations in total mitochondrial gene expression. However, the applied algorithm failed to associate these processes with characteristic alterations in expression of mitochondrial transcripts.…”

Section: Discussionmentioning

confidence: 99%

A large-scale screening of the normalized mammalian mitochondrial gene expression profiles

Anisimov

2005

Genet. Res.

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SummaryMammalian mitochondrial genomes are organized in a conserved and extremely compact manner, encoding molecules that play a vital role in oxidative phosphorylation (OXPHOS) and carry out a number of other important biological functions. A large-scale screening of the normalized mitochondrial gene expression profiles generated from publicly available mammalian serial analysis of gene expression (SAGE) datasets (over 17 . 7 millions of tags) was performed in this study. Acquired SAGE libraries represent an extensive range of human, mouse, rat, bovine and swine cell and tissue samples (normal and pathological) in a variety of conditions. Using a straightforward in silico algorithm, variations in total mitochondrial gene expression, as well as in the expression of individual genes encoded by mitochondrial genomes are addressed, and common patterns in the species-and tissue-specific mitochondrial gene expression profiles are discussed.

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“…Because the MUTZ3 cell line functions as a previously described relevant model for in vitro 19,29,30 this cell line was used for further in vitro MRP4 studies. Given the notion that a previous study by Angénieux et al 31 reported MRP4 mRNA expression in MoDC, mRNA levels were also checked by semiquantitative RT-PCR for monocytes and MUTZ3 progenitors as well as for differentiated MoDC and MUTZ3-DCs and MUTZ3-LCs. Whereas only low levels of MRP4 mRNA were detected in monocytes and MoDC, MRP4/␤-actin mRNA ratios were much higher in MUTZ3 progenitors, MUTZ3-DCs, or MUTZ3-LCs (Figure 3).…”

Section: Mrp4 Knock-down Inhibits Mutz3-lc Migration Toward Ccl19 Andmentioning

confidence: 99%

A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration

Ven

Scheffer²,

Reurs³

et al. 2008

Blood

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The capacity of dendritic cells (DCs) to migrate from peripheral organs to lymph nodes (LNs) is important in the initiation of a T cell-mediated immune response. The ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the multidrug resistance protein 1 (MRP1; ABCC1) have been shown to play a role in both human and murine DC migration. Here we show that a more recently discovered family member, MRP4 (ABCC4), is expressed on both epidermal and dermal human skin DCs and contributes to the migratory capacity of DCs. Pharmacological inhibition of MRP4 activity or downregulation through RNAi in DCs resulted in reduced migration of DCs from human skin explants and of in vitro generated Langerhans cells. The responsible MRP4 substrate remains to be identified as exogenous addition of MRP4's known substrates prostaglandin E 2 , leukotriene B 4 and D 4 , or cyclic nucleotides (all previously implicated in DC migration) could not restore migration. This notwithstanding, our data show that MRP4 is an important protein, significantly contributing to human DC migration toward the draining lymph nodes, and therefore relevant for the initiation of an immune response and a possible target for immunotherapy. IntroductionThe ATP-binding cassette (ABC) transporters were initially identified by their roles in clinical multidrug resistance (MDR) against a broad range of functionally and structurally unrelated anticancer agents. 1 Over the past 10 years, it has become apparent that several of the ABC transporters transport not only cytostatic agents but also inflammatory mediators such as platelet activating factor, 2 leukotrienes, 3 or prostaglandins. 4 Unraveling the specific roles of ABC transporters in the functioning of the immune system may therefore reveal new links for future immunotherapeutic approaches.Dendritic cells (DCs) are key initiators of the immune response, sampling their surroundings for foreign antigens. 5 They are also seen as a promising tool for targeted immunotherapeutic strategies. 6 We have shown that dendritic cell differentiation is impaired when the transporter activity of Multidrug Resistance Protein 1 (MRP1; ABCC1) is inhibited. 7 Randolph and coworkers previously reported that both P-glycoprotein (P-gp; ABCB1) and MRP1 are required for optimal DC migration. 8,9 The ABC transporter MRP4 (ABCC4) [10][11][12] is an organic anion transporter and has been described to transport prostaglandins such as PGA 2 , PGE 1 , and PGE 2 . 4 Because PGE 2 is believed to be crucial for DC migration, [13][14][15] we explored the role of this ABC transporter in DC migration. Moreover, a recent study showed that MRP4, like MRP1, can transport leukotrienes (eg, LTB 4 and LTC 4 ). 16 Thus, when expressed on DCs, MRP4 could have contributed to the original observations made for the role of MRP1 in DC migration, 9 because the used antagonist MK-571 can inhibit both transporters. In this manuscript we show that MRP4 is abundantly expressed in epidermal human skin DCs and at lower levels in dermal human ski...

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Gene induction during differentiation of human monocytes into dendritic cells: an integrated study at the RNA and protein levels

Cited by 22 publications

References 27 publications

An active mitochondrial biogenesis occurs during dendritic cell differentiation

An active mitochondrial biogenesis occurs during dendritic cell differentiation

A large-scale screening of the normalized mammalian mitochondrial gene expression profiles

A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration

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