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Influence of TNFα on the sialylation of mucins produced by a transformed cell line MM-39 derived from human tracheal gland cells

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Abstract

In order to investigate the influence of inflammation on the peripheral glycosylation of airway mucins, a human respiratory glandular cell line (MM-39) was treated by TNFα. The expression and the activity of sialyl- and fucosyl-transferases, involved in the biosynthesis of peripheral carbohydrate determinants like sialyl-Lewis x, were investigated by RT-PCR and by HPAEC respectively. The mRNA steady-state level of sialyl- (ST3Gal III) and of fucosyl- (FUT3) transferases was moderately up-regulated by TNFα; a 52% increase of α2,3-sialyltransferase activity was also observed in TNFα-stimulated MM-39 cells. After metabolic radio-labelling with [3H]glucosamine and [3H]fucose, the mucins released in␣the culture supernatant were purified by Sepharose CL-4B, density-gradient centrifugation and treatment with glycosaminoglycans-degrading enzymes. The mucins, released in the culture supernatant from control MM-39 cells, were constituted by two populations of molecules having the same 1.39–1.44 mg/ml density but carrying either high or low amounts of sialic acid residues at their periphery. TNFα was able to increase the sialylation of the weakly sialylated mucins. This effect and the enhancement of the α2,3-sialyltransferase activity by TNFα argue in favour of a regulation of the mucin sialylation by this pro-inflammatory cytokine. Despite the moderate overexpression of FUT3, no fucosylation of mucins produced by MM-39 cells was induced by TNFα. In conclusion, the influence of TNFα on the sialylation of mucins could explain why the mucins from infected patients suffering either from cystic fibrosis or from chronic bronchitis are more sialylated.

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Authors and Affiliations

  1. Unité INSERM, n° 377, place de Verdun, F-59045, Lille, France

    Philippe Delmotte, Sophie Degroote, Isabelle Van Seuningen, Annie Bernigaud, Philippe Roussel & Jean-Marc Périni

  2. EMI-INSERM 0014, Faculté de Medecine, Laboratoire de Pathologie Cellulaire et Moleculaire en Nutrition, BP 184, 9, Avenue de la Foret de Haye, 54505, Vandoeuvre-les-Nancy, France

    Marc D. Merten

  3. Faculté de Médecine, Groupe de Recherche sur les Glandes Exocrines, 27, bld Jean Moulin, F-13385, Marseille, France

    Catherine Figarella

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  1. Philippe Delmotte
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  2. Sophie Degroote
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  7. Philippe Roussel
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Delmotte, P., Degroote, S., Merten, M.D. et al. Influence of TNFα on the sialylation of mucins produced by a transformed cell line MM-39 derived from human tracheal gland cells. Glycoconj J 18, 487–497 (2001). https://doi.org/10.1023/A:1016038219183

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