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Fibroblasts Impact Goblet Cell Responses to Lactic Acid Bacteria After Exposure to Inflammatory Cytokines and Mucus Disruptors.

ABSTRACT: SCOPE:Mucus produced by goblet cells contributes to gut barrier function. Lactic acid bacteria (LAB) have been shown to impact mucus production. It is not completely known whether mucus production is influenced by the abundantly present fibroblasts in the intestine. METHODS AND RESULTS:The influence of fibroblasts on mucus-related genes including mucin-2 (MUC2), trefoil factor 3 (TFF3), resistin-like molecule ? (RETNLB), carbohydrate sulfotransferase 5 (CHST5), and galactose-3-O-sulfotransferase 2 (GAL3ST2) is examined after co-culture of LS174T-goblet cells and CCD-18Co colonic fibroblasts in the presence and absence of LAB-strains known to impact mucus function. This is also tested after exposure to TNF-?, IL-13, or the mucin synthesis inhibitor tunicamycin (Tm). Effects of fibroblasts are treatment duration- and bacterial species-dependent under homeostatic conditions. During TNF-? challenge, fibroblasts reverse Lactobacillus (L.) rhamnosus CCFM237-elicited declined TFF3 expression. After IL-13 exposure, L. rhamnosus CCFM237 and L. fermentum CCFM787 attenuate enhanced TFF3 and RETNLB expression, respectively, only in the presence of fibroblasts. LAB has no effects on Tm-induced decreased expression of goblet cell-related genes regardless of the presence of fibroblasts. CONCLUSION:It is demonstrated that goblet cell-fibroblast crosstalk impacts mucus synthesis and influences the effects of LAB on goblet cell-related genes. Effects are LAB-species and stressor dependent.

SUBMITTER: Ren C

PROVIDER: S-EPMC6618108 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Fibroblasts Impact Goblet Cell Responses to Lactic Acid Bacteria After Exposure to Inflammatory Cytokines and Mucus Disruptors.

Ren Chengcheng C Dokter-Fokkens Jelleke J Figueroa Lozano Susana S Zhang Qiuxiang Q de Haan Bart J BJ Zhang Hao H Faas Marijke M MM de Vos Paul P

Molecular nutrition & food research 20190422 12

<h4>Scope</h4>Mucus produced by goblet cells contributes to gut barrier function. Lactic acid bacteria (LAB) have been shown to impact mucus production. It is not completely known whether mucus production is influenced by the abundantly present fibroblasts in the intestine.<h4>Methods and results</h4>The influence of fibroblasts on mucus-related genes including mucin-2 (MUC2), trefoil factor 3 (TFF3), resistin-like molecule β (RETNLB), carbohydrate sulfotransferase 5 (CHST5), and galactose-3-O-s ...[more]

PMID: 30977971

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Project description:Quiescent cells are considered to be dormant. However, recent studies suggest that quiescent fibroblasts possess active metabolic profile and certain functional characteristics. We previously observed that serum-starved quiescent fibroblasts respond to proinflammatory stimuli by robust expression of cyclooxygenase-2 (COX-2), which declines after the quiescent fibroblasts are driven to proliferation. In this study, we elucidated the underlying signaling and transcriptional mechanism and identified by microarray genes with similar differential expression. By using pharmacological inhibitors coupled with gene silencing, we uncovered the key role of protein kinase C ? (PKC?) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling in mediating COX-2 expression in quiescent cells. Surprisingly, COX-2 expression in proliferative cells was not blocked by PKC? or ERK1/2 inhibitors due to intrinsic inhibition of PKC? and ERK1/2 in proliferative cells. Restrained COX-2 transcription in proliferative cells was attributable to reduced NF-?B binding. Microarray analysis identified 35 genes whose expressions were more robust in quiescent than in proliferative cells. A majority of those genes belong to proinflammatory cytokines, chemokines, adhesive molecules and metalloproteinases, which require NF-?B for transcription. Quiescent fibroblasts had a higher migratory activity than proliferative fibroblasts as determined by the transwell assay. Selective COX-2 inhibition reduced migration which was restored by prostaglandin E(2). As COX-2 and inflammatory mediators induce DNA oxidation, we measured 8-hydroxydeoxyguanosine (8-OHdG) in quiescent vs. proliferative fibroblasts. PMA-induced 8-OHdG accumulation was significantly higher in quiescent than in proliferative fibroblasts. These findings indicate that quiescent fibroblasts (and probably other quiescent cells) are at the forefront in mounting inflammatory responses through expression of an array of proinflammatory genes via the PKC?/ERK1/2 signaling pathway.

Dataset Information

Fibroblasts Impact Goblet Cell Responses to Lactic Acid Bacteria After Exposure to Inflammatory Cytokines and Mucus Disruptors.

Publications

Fibroblasts Impact Goblet Cell Responses to Lactic Acid Bacteria After Exposure to Inflammatory Cytokines and Mucus Disruptors.

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