Activation of mucin exocytosis and upregulation of MUC genes in polarized human intestinal mucin-secreting cells by the thiol-activated exotoxin listeriolysin O.
The secreted thiol-activated cytolysin listeriolysin O (LLO) was responsible for L. monocytogenes-induced high-molecular glycoproteins (HMGs) exocytosis in cultured human mucosecreting HT29-MTX cells. By biochemical analysis we demonstrate that the majority of secreted HMGs in LLO-stimulated cells are of mucin origin. In parallel, analysis of the expression of MUCs genes showed that the transcription of the MUC3, MUC4 and MUC12 genes encoding for membrane-bound mucins was increased in LLO-stimulated cells. Upregulation of the MUC3 gene correlates with an increased expression of the membrane-bound MUC3 mucin. In contrast, increase in secretion of the gel-forming MUC5AC mucin develops without upregulation of the MUC5AC gene. Finally, results showed that NF-kappaB and AP-1 transcription factors were not involved in LLO-induced upregulation of MUCs genes in HT29-MTX cells, whereas L. monocytogenes infection was able to promote the degradation of IkappaB proteins in the cells.
Liévin-Le Moal
Vanessa
V
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 510, Pathogènes et Fonctions des Cellules Epithéliales Polarisées, Faculté de Pharmacie Paris XI, F-92296 Châtenay-Malabry, France.
Huet
Guillemette
G
Aubert
Jean-Pierre
JP
Bara
Jacques
J
Forgue-Lafitte
Marie-Elisabeth
ME
Servin
Alain L
AL
Coconnier
Marie-Hélène
MH
D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins; D002460:Cell Line; D016764:Cell Polarity; D003603:Cytotoxins / Q000378:metabolism; D005089:Exocytosis; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006460:Hemolysin Proteins; D006801:Humans; D051550:I-kappa B Kinase; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D009077:Mucins / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D016209:Interleukin-8; D009077:Mucins; D016328:NF-kappa B; D009841:Oligonucleotides; D011509:Proteoglycans; D018808:Transcription Factor AP-1; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C038705:hlyA protein, Listeria monocytogenes