985 - Human Long Non-Coding RNA (LNCRNA) CCAT1 and UCA1 Regulate Proinflammatory Response and Cell Migration in Human and Mouse Intestinal Epithelial Cells

2018 ◽  
Vol 154 (6) ◽  
pp. S-183-S-184 ◽  
Author(s):  
Ivy Ka Man Law ◽  
David M. Padua ◽  
Dimitrios Iliopoulos ◽  
Charalabos Pothoulakis
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Proinflammatory Response ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Human And Mouse

scholarly journals miR-222 represses expression of zipcode binding protein-1 and phospholipase C-γ1 in intestinal epithelial cells

2019 ◽  
Vol 316 (3) ◽  
pp. C415-C423 ◽  
Author(s):  
Li-Ping Jiang ◽  
Shelley R. Wang ◽  
Hee Kyoung Chung ◽  
Saharsh Buddula ◽  
Jian-Ying Wang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Phospholipase C ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Acute Injury ◽  
Intestinal Epithelial ◽  
Small Interfering Rnas ◽  
The Stability ◽  
Wounded Area

Both zipcode binding protein-1 (ZBP1) and phospholipase C-γ1 (PLCγ1) are intimately involved in many aspects of early intestinal mucosal repair after acute injury, but the exact mechanisms that control their cellular abundances remain largely unknown. The present study shows that microRNA-222 (miR-222) interacts with the mRNAs encoding ZBP1 and PLCγ1 and regulates ZBP1 and PLCγ1 expression in intestinal epithelial cells (IECs). The biotinylated miR-222 bound specifically to the ZBP1 and PLCγ1 mRNAs in IECs. Ectopically expressed miR-222 precursor destabilized the ZBP1 and PLCγ1 mRNAs and consequently lowered the levels of cellular ZBP1 and PLCγ1 proteins. Conversely, decreasing the levels of cellular miR-222 by transfection with its antagonism increased the stability of the ZBP1 and PLCγ1 mRNAs and increased the levels of ZBP1 and PLCγ1 proteins. Overexpression of miR-222 also inhibited cell migration over the wounded area, which was partially abolished by overexpressing ZBP1 and PLCγ1. Furthermore, prevention of the increased levels of ZBP1 and PLCγ1 in the miR-222-silenced cells by transfection with specific small interfering RNAs targeting ZBP1 or PLCγ1 mRNA inhibited cell migration after wounding. These findings indicate that induced miR-222 represses expression of ZBP1 and PLCγ1 at the posttranscriptional level, thus inhibiting IEC migration during intestinal epithelial restitution after wounding.

Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells

2007 ◽  
Vol 292 (3) ◽  
pp. G767-G778 ◽  
Author(s):  
Jun Sun ◽  
Pamela E. Fegan ◽  
Anjali S. Desai ◽  
James L. Madara ◽  
Michael E. Hobert
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Prior Exposure ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
Proinflammatory Response ◽  
Gram Negative ◽  
Human Intestinal Epithelial Cells ◽  
Induced Tolerance ◽  
Toll Like Receptor 5

Salmonella typhimurium is a gram-negative enteric pathogen that invades the mucosal epithelium and is associated with diarrheal illness in humans. Flagellin from S. typhimurium and other gram-negative bacteria has been shown to be the predominant proinflammatory mediator through activation of the basolateral Toll-like receptor 5 (TLR5). Recent evidence has shown that prior exposure can render immune cells tolerant to subsequent challenges by TLR ligands. Accordingly, we examined whether prior exposure to purified flagellin would render human intestinal epithelial cells insensitive to future contact. We found that flagellin-induced tolerance is common to polarized epithelial cells and prevents further activation of proinflammatory signaling cascades by both purified flagellin and Salmonella bacteria but does not affect TNF-α stimulation of the same pathways. Flagellin tolerance is a rapid process that does not require protein synthesis, and that occurs within 1 to 2 h of flagellin exposure. Prolonged flagellin exposure blocks activation of the NF-κB, MAPK, and phosphoinositol 3-kinase signaling pathways and results in the internalization of a fraction of the basolateral TLR5 without affecting the polarity or total expression of TLR5. After removal of flagellin, cells require more than 24 h to fully recover their ability to mount a normal proinflammatory response. We have found that activation of phosphoinositol 3-kinase and Akt by flagellin has a small damping effect in the early stages of flagellin signaling but is not responsible for tolerance. Our study indicates that inhibition of TLR5-associated IL-1 receptor-associated kinase-4 activity occurs during the development of flagellin tolerance and is likely to be the cause of tolerance.

TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding

2006 ◽  
Vol 290 (4) ◽  
pp. G782-G792 ◽  
Author(s):  
Jaladanki N. Rao ◽  
Oleksandr Platoshyn ◽  
Vera A. Golovina ◽  
Lan Liu ◽  
Tongtong Zou ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Transient Receptor Potential ◽  
Intestinal Epithelial Cells ◽  
Critical Role ◽  
Receptor Potential ◽  
Mucosal Injury ◽  
Intestinal Epithelial ◽  
Epithelial Restitution ◽  
Transient Receptor

An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) results from Ca2+ release from intracellular stores and extracellular Ca2+ influx through Ca2+-permeable ion channels and is crucial for initiating intestinal epithelial restitution to reseal superficial wounds after mucosal injury. Capacitative Ca2+ entry (CCE) induced by Ca2+ store depletion represents a major Ca2+ influx mechanism, but the exact molecular components constituting this process remain elusive. This study determined whether canonical transient receptor potential (TRPC)1 served as a candidate protein for Ca2+-permeable channels mediating CCE in intestinal epithelial cells and played an important role in early epithelial restitution. Normal intestinal epithelial cells (the IEC-6 cell line) expressed TRPC1 and TPRC5 and displayed typical records of whole cell store-operated Ca2+ currents and CCE generated by Ca2+ influx after depletion of intracellular stores. Induced TRPC1 expression by stable transfection with the TRPC1 gene increased CCE and enhanced cell migration during restitution. Differentiated IEC-Cdx2L1 cells induced by forced expression of the Cdx2 gene highly expressed endogenous TRPC1 and TRPC5 and exhibited increased CCE and cell migration. Inhibition of TRPC1 expression by small interfering RNA specially targeting TRPC1 not only reduced CCE but also inhibited cell migration after wounding. These findings strongly suggest that TRPC1 functions as store-operated Ca2+ channels and plays a critical role in intestinal epithelial restitution by regulating CCE and intracellular [Ca2+]cyt.

JAK/STAT3 Pathway in Human Intestinal Epithelial Cells During Trefoil Factor 3(TFF3) Mediated Cell Migration

2020 ◽  
Vol 17 (8) ◽  
pp. 993-1000
Author(s):  
Mengmeng Zhuang ◽  
Juan Le ◽  
Bo Zhu ◽  
Wenwen Zhang ◽  
Hao Yan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Matrix Metalloproteinases ◽  
Intestinal Epithelial Cells ◽  
The Body ◽  
Intestinal Epithelial ◽  
Trefoil Factor ◽  
Stat3 Pathway ◽  
Ht 29 ◽  
E Cadherin

Objective: Trefoil factor family is expressed in several tissues of the body and provides gastric and intestinal protection and healing. This research aims to indicate the mechanism involved in its function. Methods: The intestinal epithelial cells were pretreated with JAK inhibitor AG490 or the concentration of 60ug/ml human recombinant trefoil factor, while the levels of phospho-STAT3, E-cadherin and N-cadherin were detected by Western Blotting. The levels of Matrix Metalloproteinases, Ecadherin and N-cadherin were evaluated by quantitative real time PCR. The cell migration was assessed by the transwell assay and the scratch assay. The immunofluorescence method was performed to detect the reduction of molecular E-cadherin. Results: hTFF3 activates the JAK/STAT3 pathway in HT-29 cells. The effect of JAK/STAT3 pathway mechanism on cell migration promoted by hTFF3. TFF3 promoting cell migration is associated with increased gene transcription of MMPs. hTFF3 alters E-cadherin expression. hTFF3 activates the expression of N-cadherin and down-regulates E-cadherin expression in HT-29 Cells. Conclusion: We have shown that TFF3 activated the JAK/STAT3 pathway. TFF3 increased the level of Matrix Metalloproteinases and N-cadherin, decreased that of E-cadherin, while AG490 had the opposite effect. TFF3 accelerated cell migration and the AG490 relieved the migrating rate to control the levels. TFF3 activated JAK/STAT3 pathway which was associated with intestinal epithelial cell migration.

PKCζ participates in activation of inflammatory response induced by enteropathogenicE. coli

2003 ◽  
Vol 285 (3) ◽  
pp. C512-C521 ◽  
Author(s):  
Suzana D. Savkovic ◽  
Athanasia Koutsouris ◽  
Gail Hecht
Keyword(s):  
Epithelial Cells ◽  
Kinase Activity ◽  
Intestinal Epithelial Cells ◽  
Fold Increase ◽  
Serine Phosphorylation ◽  
Intestinal Epithelial ◽  
Proinflammatory Response ◽  
Independent Events ◽  
Iκb Kinase ◽  
Iκbα Phosphorylation

We showed previously that enteropathogenic Escherichia coli (EPEC) infection of intestinal epithelial cells induces inflammation by activating NF-κB and upregulating IL-8 expression. We also reported that extracellular signal-regulated kinases (ERKs) participate in EPEC-induced NF-κB activation but that other signaling molecules such as PKCζ may be involved. The aim of this study was to determine whether PKCζ is activated by EPEC and to investigate whether it also plays a role in EPEC-associated inflammation. EPEC infection induced the translocation of PKCζ from the cytosol to the membrane and its activation as determined by kinase activity assays. Inhibition of PKCζ by the pharmacological inhibitor rottlerin, the inhibitory myristoylated PKCζ pseudosubstrate (MYR-PKCζ-PS), or transient expression of a nonfunctional PKCζ significantly suppressed EPEC-induced IκBα phosphorylation. Although PKCζ can activate ERK, MYR-PKCζ-PS had no effect on EPEC-induced stimulation of this pathway, suggesting that they are independent events. PKCζ can regulate NF-κB activation by interacting with and activating IκB kinase (IKK). Coimmunoprecipitation studies showed that the association of PKCζ and IKK increased threefold 60 min after infection. Kinase activity assays using immunoprecipitated PKCζ-IKK complexes from infected intestinal epithelial cells and recombinant IκBα as a substrate showed a 2.5-fold increase in IκBα phosphorylation. PKCζ can also regulate NF-κB by serine phosphorylation of the p65 subunit. Serine phosphorylation of p65 was increased after EPEC infection but could not be consistently attenuated by MYR-PKCζ-PS, suggesting that other signaling events may be involved in this particular arm of NF-κB regulation. We speculate that EPEC infection of intestinal epithelial cells activates several signaling pathways including PKCζ and ERK that lead to NF-κB activation, thus ensuring the proinflammatory response.

scholarly journals Effects of Si-Jun-Zi decoction polysaccharides on cell migration and gene expression in wounded rat intestinal epithelial cells

2005 ◽  
Vol 93 (1) ◽  
pp. 21-29 ◽  
Author(s):  
L. Liu ◽  
L. Han ◽  
Daisy Y. L. Wong ◽  
Patrick Y. K. Yue ◽  
W. Y. Ha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Optimal Dose ◽  
Intestinal Epithelial ◽  
Active Components ◽  
Chinese Herbal ◽  
Herbal Prescription

Si-Jun-Zi decoction (SJZD), a traditional Chinese herbal prescription, has been used clinically for treating patients with disorders of the digestive system. Previous studies indicated that the polysaccharides of SJZD (SJZPS) are the active components contributing towards its pharmacological effects in improving gastrointestinal function and immunity. However, the protective and restitutive effects on intestinal epithelial cells remain unknown. In the present study, SJZPS were first extracted and chemically characterized. Then their stimulatory and restitutive effects on intestinal epithelial cells (IEC-6 cells) were elicited by different in vitro models including migration of wounded IEC-6 cells and cell proliferation. Results indicated that SJZPS not only protects the cells against the harmful impairment of indomethacin but also enhances re-epithelialization of a wounded monolayer at an optimal dose of 100 μg/ml at 24 h incubation. To elucidate the modulatory effect of SJZPS on wounded IEC-6 cells at the molecular level, an oligonucleotide microarray was employed to study differential gene expression of SJZPS-treated IEC-6 cells and the candidate genes were validated by RT-PCR. There was increased expression of genes coding for ion channels and transporters, which are critical to cell migration and restoration of wounded intestinal cells, suggesting a possible mechanism for re-epithelialization. In conclusion, our data show for the first time that SJZPS can enhance intestinal restitution and protect against indomethacin-induced damage of intestinal epithelial cells. These findings provide new insight into the mechanism of action of a traditional Chinese herbal prescription, SJZD, in intestinal wound restitution.

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