TNF regulates sialyl-Lewisx and 6-sulfo-sialyl-Lewisx expression in human lung through up-regulation of ST3GAL4 transcript isoform BX

Colomb, Florent; Krzewinski-Recchi, Marie-Ange; Machhour, Fala El; Mensier, E; Jaillard, Sophie; Steenackers, Agata; Harduin-Lepers, Anne; Lafitte, Jean-Jacques; Delannoy, Philippe; Groux-Degroote, Sophie

doi:10.1016/j.biochi.2012.05.030

Cited by 27 publications

(45 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another mechanism is suppression of synthesis of galactose-containing glycans. Recent reports showed that treatment with proinflammatory cytokines (IL-1 and TNFα) affects the expression of glycosyltransferases and leads to glycan changes in mammals (38,39). Therefore, the activation of Toll signaling by infection may also involve regulation of the activity of as-yet-unidentified galactosyltransferases and/or enzymes that are required for UDP-galactose biosynthesis, although the level of senju mRNA in the Tl 10B -expressing flies was unchanged (Fig.…”

Section: Discussionmentioning

confidence: 95%

Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation

Yamamoto-Hino

Muraoka

Kondo

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The innate immune system is the first line of defense encountered by invading pathogens. Delayed and/or inadequate innate immune responses can result in failure to combat pathogens, whereas excessive and/or inappropriate responses cause runaway inflammation. Therefore, immune responses are tightly regulated from initiation to resolution and are repressed during the steady state. It is well known that glycans presented on pathogens play important roles in pathogen recognition and the interactions between host molecules and microbes; however, the function of glycans of host organisms in innate immune responses is less well known. Here, we show that innate immune quiescence and strength of the immune response are controlled by host glycosylation involving a novel UDPgalactose transporter called Senju. In senju mutants, reduced expression of galactose-containing glycans resulted in hyperactivation of the Toll signaling pathway in the absence of immune challenges. Genetic epistasis and biochemical analyses revealed that Senju regulates the Toll signaling pathway at a step that converts Toll ligand Spatzle to its active form. Interestingly, Toll activation in immune-challenged wild type (WT) flies reduced the expression of galactose-containing glycans. Suppression of the degalactosylation by senju overexpression resulted in reduced induction of Toll-dependent expression of an antimicrobial peptide, Drosomycin, and increased susceptibility to infection with Gram-positive bacteria. These data suggest that Senju-mediated galactosylation suppresses undesirable Toll signaling activation during the steady state; however, Toll activation in response to infection leads to degalactosylation, which raises the immune response to an adequate level and contributes to the prompt elimination of pathogens.innate immunity | glycosylation | Toll pathway | nucleotide sugar transporter | galactose

show abstract

Section: Discussionmentioning

confidence: 95%

Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation

Yamamoto-Hino

Muraoka

Kondo

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Cells were washed three times in PBS, scraped, collected by centrifugation (2000 g for 5 min at 4 • C) and total proteins were extracted as described previously [5], with the additional use of phosphatase inhibitor cocktail in lysis buffer (Thermo Fischer Scientific). A 20 μg aliquot of protein was boiled for 10 min in reducing Laemmli sample buffer and resolved by SDS/PAGE (10 % minigels).…”

Section: Mapk Phosphorylation Analysismentioning

confidence: 99%

“…It is well documented that inflammation, via pro-inflammatory cytokines, modifies the expression and the activity of fucosyl-, sialyl-and sulfo-transferases involved in terminal glycan chain biosynthesis. In particular, we and others have shown, that in human bronchial mucosa and lung epithelial cells, TNF (tumour necrosis factor) induced the expression of the mucin-associated sLe x and 6-sulfo-sLe x epitopes [5][6][7]. We recently identified ST3Gal IV as the main α2,3-sialyltransferase responsible for the biosynthesis of sLe x and 6-sulfo-sLe x in bronchial mucosa [5].…”

Section: Introductionmentioning

confidence: 96%

“…In particular, we and others have shown, that in human bronchial mucosa and lung epithelial cells, TNF (tumour necrosis factor) induced the expression of the mucin-associated sLe x and 6-sulfo-sLe x epitopes [5][6][7]. We recently identified ST3Gal IV as the main α2,3-sialyltransferase responsible for the biosynthesis of sLe x and 6-sulfo-sLe x in bronchial mucosa [5]. The ST3GAL4 (ST3 β-galactoside α-2,3-sialyltransferase 4) gene that encodes the sialyltransferase ST3Gal IV is localized on chromosome 11(q23-q24) and distributed over 14 exons.…”

Section: Introductionmentioning

confidence: 98%

“…It produces at least five transcripts by a combination of alternative splicing and alternative promoter utilization, which code for identical protein sequences except at the 5 -ends [8]. We have shown that, in both human bronchial explants and A549 lung cancer cells, TNF regulates the expression of the BX-specific transcript of ST3GAL4 [5].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TNF induces the expression of the sialyltransferase ST3Gal IV in human bronchial mucosa via MSK1/2 protein kinases and increases FliD/sialyl-Lewisx-mediated adhesion of Pseudomonas aeruginosa

Colomb

Vidal

Bobowski

et al. 2013

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

We have shown previously that the pro-inflammatory cytokine TNF (tumour necrosis factor) could drive sLe(x) (sialyl-Lewis(x)) biosynthesis through the up-regulation of the BX transcript isoform of the ST3GAL4 (ST3 β-galactoside α-2,3-sialyltransferase 4) sialyltransferase gene in lung epithelial cells and human bronchial mucosa. In the present study, we show that the TNF-induced up-regulation of the ST3GAL4 BX transcript is mediated by MSK1/2 (mitogen- and stress-activated kinase 1/2) through the ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and increases sLe(x) expression on high-molecular-mass glycoproteins in inflamed airway epithelium. We also show that the TNF-induced sLe(x) expression increases the adhesion of the Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial cells in a FliD-dependent manner. These results suggest that ERK and p38 MAPK, and the downstream kinase MSK1/2, should be considered as potential targets to hamper inflammation, bronchial mucin glycosylation changes and P. aeruginosa binding in the lung of patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis.

show abstract

ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 4 (ST3GAL4)

Schnaar

2014

Handbook of Glycosyltransferases and Related Genes

View full text Add to dashboard Cite

TNF regulates sialyl-Lewisx and 6-sulfo-sialyl-Lewisx expression in human lung through up-regulation of ST3GAL4 transcript isoform BX

Cited by 27 publications

References 35 publications

Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation

Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation

TNF induces the expression of the sialyltransferase ST3Gal IV in human bronchial mucosa via MSK1/2 protein kinases and increases FliD/sialyl-Lewisx-mediated adhesion of Pseudomonas aeruginosa

ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 4 (ST3GAL4)

Contact Info

Product

Resources

About