IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cultured Conjunctival Goblet Cells

Henriksson, Johanna Tukler; Coursey, Terry G.; Corry, David B.; Paiva, Cintia S. de; Pflugfelder, Stephen C.

doi:10.1167/iovs.14-15496

Cited by 95 publications

(90 citation statements)

References 58 publications

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“…Analyses of the GO categories included several genes, which are relevant to cell proliferation, cell migration and invasion. As evidence has suggested that S100A6 regulates the levels of certain genes involved in cell proliferation, including IL-8 (24), IL-2 (25), IL-13 (26), IL-6R (27), CDK4 (28), CDK5 (29), MCM7 (30), Bcl2 (29) and MYC (31), these genes were selectively assessed. To confirm and to evaluate their expression levels, mRNA quantification was performed.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of S100A6 promotes cell proliferation in gastric cancer cells

Wang

Lin

et al. 2016

Oncology Letters

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S100A6 is involved in regulating the progression of cancer. S100A6 can regulate the dynamics of cytoskeletal constituents, cell growth and differentiation by interacting with binding or target proteins. The present study investigated whether S100A6 affects cell proliferation in gastric cancer cells by stimulating several downstream factors. Firstly, the expression and localization of S100A6 were investigated using immunohistochemical staining, an immunoelectron microscopy and laser confocal scanning. A ChIP-Chip assay was performed to determine the downstream factors of S100A6 using promoter Chip analysis, including approximately the −800 to +200 regions around the transcription starting point. Polymerase chain reaction analysis was performed to confirm this. It was found that the intensity of S100A6 staining was markedly higher in the cytoplasm and nucleus, and its expression level correlated with that of the Ki67 protein. The overexpression of S100A6 also promoted cell proliferation in AGS and BGC823 cell lines, detected using a Cell Counting-Kit 8 assay. In cells overexpressing S100A6, the expression levels of interleukin (IL)-8, cyclin-dependent kinase (CDK)5, CDK4, minichromosome maintenance complex component 7 (MCM7) and B-cell lymphoma 2 (Bcl2) were noticeably increased. In conclusion, the increased expression of S100A6 promoted cell proliferation by regulating the expression levels of IL-8, CDK5, CDK4, MCM7 and Bcl2 in gastric cancer cells.

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Section: Discussionmentioning

confidence: 99%

Increased expression of S100A6 promotes cell proliferation in gastric cancer cells

Wang

Lin

et al. 2016

Oncology Letters

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“…They also produce factors that maintain homeostasis and immune tolerance on the ocular surface. 109, 179 The worst cornea disease develops in dry eye conditions with loss of goblet cells, such as Sjögren syndrome, Stevens-Johnson syndrome and graft-vs.-host disease. 134, 180, 181 The Th1 cytokine IFN-γ inhibits goblet cell secretion and promotes apoptosis of these cells.…”

Section: Future Directions For Researchmentioning

confidence: 99%

The Pathophysiology of Dry Eye Disease

2017

Self Cite

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Clinical and laboratory studies performed over the past few decades have discovered that dry eye is a chronic inflammatory disease that can be initiated by numerous extrinsic or intrinsic factors that promote an unstable and hyperosmolar tear film. These changes in tear composition, in some cases combined with systemic factors, lead to an inflammatory cycle that causes ocular surface epithelial disease and neural stimulation. Acute desiccation activates stress signaling pathways in the ocular surface epithelium and resident immune cells. This triggers production of innate inflammatory mediators that stimulate the production of matrix metalloprotease, inflammatory cell recruitment, and dendritic cell maturation. These mediators combined with exposure of autoantigens can lead to an adaptive T-cell mediated response. Cornea barrier disruption develops by protease-mediated lysis of epithelial tight junctions leading to accelerated cell death, desquamation, an irregular poorly lubricated cornea surface and exposure and sensitization of epithelial nociceptors. Conjunctival goblet cell dysfunction and death are promoted by the T helper 1 cytokine interferon gamma (IFN-γ). These epithelial changes further destabilize the tear film, amplify inflammation and create a vicious cycle. Cyclosporine and lifitegrast, the two FDA-approved therapies inhibit T cell activation and cytokine production. While these therapies represent a major advance in dry eye therapy, they are not effective in improving discomfort and corneal epithelial disease in all patients. Preclinical studies have identified other potential therapeutic targets, biomarkers and strategies to bolster endogenous immunoregulatory pathways. These discoveries will hopefully lead to further advances in diagnostic classification and treatment.

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“…Immunohistochemical assay of the keratin has been subsequently used to identify goblet cells in cultures of conjunctival epithelial cells (Shatos et al, 2001; Tukler Henriksson et al, 2015). In recent comparative microarray studies of conjunctival RNA from wild type mice and Spdef null mice lacking goblet cells, no change in keratin 7-gene expression could be found with the loss of the goblet cells suggesting that the keratin may not be goblet cell specific (Marko et al, 2013).…”

Section: Goblet Cell Products and Specific Cell Markersmentioning

confidence: 99%

“…Histology of these cells show stratified layers of cells that do not appear to be polarized nor does one see in published figures a mucin granule filled cytoplasm. Thus the cells of the culture system lack classic goblet cell morphology (Contreras-Ruiz and Masli, 2015; Shatos et al, 2001; Tukler Henriksson et al, 2015). …”

Section: Models For Study Of Goblet Cell Function/biologymentioning

confidence: 99%

Goblet cells of the conjunctiva: A review of recent findings

Gipson

2016

Progress in Retinal and Eye Research

197

127

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Goblet cells within the conjunctival epithelium are specialized cells that secrete mucins onto the surface of the eye. Recent research has demonstrated new characteristics of the cells, including factors influencing their differentiation, their gene products and their functions at the ocular surface. The following review summarizes the newly discovered aspects of the role of Spdef, a member of the Ets transcription factor family in conjunctival goblet cell differentiation, the newly discovered goblet cell products including claudin2, the Wnt inhibitor Frzb, and the transmembrane mucin Muc16. The current concepts of conjunctival goblet cell function, including debris removal and immune surveillance are reviewed, as are changes in the goblet cell population in ocular surface diseases. Major remaining questions regarding conjunctival cell biology are discussed.

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IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cultured Conjunctival Goblet Cells

Cited by 95 publications

References 58 publications

Increased expression of S100A6 promotes cell proliferation in gastric cancer cells

Increased expression of S100A6 promotes cell proliferation in gastric cancer cells

The Pathophysiology of Dry Eye Disease

Goblet cells of the conjunctiva: A review of recent findings

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