Inflammatory cues modulate the expression of secretory product genes, Golgi sulfotransferases and sulfomucin production in LS174T cells.

Abstract

The signals that mediate goblet cell expression of specific mucin chemotypes are poorly defined. Animal and in vitro studies show that acidomucin chemotypes may be altered by inflammation and changes in intestinal microbiota. To examine factors that may elicit this response, human adenocarcinoma-derived LS174T cells, which have a goblet cell-like phenotype and produce both sulfo- and sialomucins, were used to examine the effects of selected microbial and host factors on expression of goblet cell secretory product genes, sulfotransferases and sulfomucin production. Expression of genes encoding mucin 2 (MUC2), resistin-like molecule β (RETNLB), and trefoil factor 3 (TFF3) and Golgi sulfotransferases, carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 (CHST5) and galactose-3-O-sulfotransferase 2 (GAL3ST2), was measured by quantitative reverse transcriptase-polymerase chain reaction following treatment with bacterial flagellin, tumor necrosis factor α (TNF-α) or the mucogenic cytokine interleukin-13 (IL-13). Expression of the toll-like receptor 5 (TLR5) gene was also analysed. Sulfomucin expression was examined via high-iron diamide/alcian blue (HID/AB) histochemistry and immunofluorescent staining for the Sulfo Le(a) antigen, which is synthesized in part by GAL3ST2. Flagellin, IL-13 and TNF-α all significantly increased GAL3ST2, MUC2, TFF3 and TLR5 expression, while only IL-13 increased RETNLB and CHST5 expression. Based on HID/AB histochemistry, mucin sulfation was significantly increased in response to both flagellin and IL-13 but not TNF-α. Only treatment with flagellin increased the expression of the Sulfo Le(a) antigen. Collectively, these results indicate that bacterial flagellin, IL-13 and TNF-α differentially modulate the expression of goblet cell secretory product genes, sulfotransferases and sulfomucin production.

• Authors: Jennifer A Croix, Shikha Bhatia, H Rex Gaskins
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 236 Issue 12 Pg. 1402-12 (Dec 2011) ISSN: 1535-3699 [Electronic] England
• PMID: 22101519 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Inflammation Mediators
• Interleukin-13
• Interleukin-8
• Mucins
• TLR5 protein, human
• Toll-Like Receptor 5
• Tumor Necrosis Factor-alpha
• sulfomucin
• Flagellin
• Sulfurtransferases
• GAL3ST2 protein, human
• Sulfotransferases
• carbohydrate sulfotransferases

Topics

• Cell Line, Tumor
• Flagellin (pharmacology)
• Humans
• Inflammation Mediators (pharmacology)
• Interleukin-13 (pharmacology)
• Interleukin-8 (metabolism)
• Mucins (biosynthesis)
• Sulfotransferases (metabolism)
• Sulfurtransferases (metabolism)
• Toll-Like Receptor 5 (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)