scholarly journals Experimental Cell Line Models for Nephrotoxicity Screening

2021 ◽  
Vol 11 (3) ◽  
pp. 160-166
Author(s):  
I. A. Mazerkina ◽  
V. A. Evteev ◽  
A. B. Prokofiev ◽  
O. V. Muslimova ◽  
E. Yu. Demchenkova
Keyword(s):  
Epithelial Cell ◽  
Proximal Tubule ◽  
Cell Lines ◽  
Test Methods ◽  
Renal Proximal Tubule ◽  
Cell Models ◽  
Proximal Tubule Epithelial Cell ◽  
Epithelial Cell Lines

The aim of the study was to review literature data on cell models for experimental assessment of drug nephrotoxicity in vitro. Because of nephrotoxicity, 2% of new investigational medicinal products are discarded at the stage of preclinical in vivo studies in laboratory animals, and 19%—after phase 3 clinical trials. Prediction of toxicity in cell models could make drug development more cost-effective and help to reduce/avoid animal testing. At present, there are no official international guidelines for assessment of nephrotoxicity in vitro, but there is a lot of research underway. The main toxicity target in kidneys is renal proximal tubule epithelial cells, therefore the main research is focused on the development of renal proximal tubule epithelial cell lines with stable functional characteristics. Another important aspect in nephrotoxicity modeling is the choice of relevant test methods and end points which would reflect potential toxicity mechanisms. The paper reviews existing human renal proximal tubule epithelial cell lines and current test methods for assessing cytotoxicity. Promising areas for future development of cell models for nephrotoxicity assessment— are optimisation and standardisation of in vitro systems that would help to make preclinical predictions of drug nephrotoxicity in vivo.  

scholarly journals In Vivo and In Vitro Studies of Cytosolic Phospholipase A2 Expression in Helicobacter pyloriInfection

2001 ◽  
Vol 69 (9) ◽  
pp. 5857-5863 ◽  
Author(s):  
Gerardo Nardone ◽  
Eileen L. Holicky ◽  
James R. Uhl ◽  
Lina Sabatino ◽  
Stefania Staibano ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Protein Expression ◽  
Cell Lines ◽  
Cellular Adhesion ◽  
Cancer Pathogenesis ◽  
Cellular Expression ◽  
Epithelial Cell Lines ◽  
H Pylori

ABSTRACT Modifications of mucosal phospholipids have been detected in samples from patients with Helicobacter pylori-positive gastritis. These alterations appear secondary to increased phospholipase A2 activity (PLA2). The cytosolic form of this enzyme (cPLA2), normally involved in cellular signaling and growth, has been implicated in cancer pathogenesis. The aim of this study was to investigate cPLA2 expression and PLA2 activity in the gastric mucosae of patients with and without H. pylori infection. In gastric biopsies from 10H. pylori-positive patients, cPLA2 levels, levels of mRNA as determined by reverse transcriptase PCR, levels of protein as determined by immunohistochemistry, and total PLA2 activity were higher than in 10 H. pylori-negative gastritis patients. To clarify whether H. pylori had a direct effect on the cellular expression of cPLA2, we studied cPLA2 expression in vitro with different human epithelial cell lines, one from a patient with larynx carcinoma (i.e., HEp-2 cells) and two from patients with gastric adenocarcinoma (i.e., AGS and MKN 28 cells), incubated with differentH. pylori strains. The levels of cPLA2, mRNA, and protein expression were unchanged in Hep-2 cells independently of cellular adhesion or invasion of the bacteria. Moreover, no change in cPLA2 protein expression was observed in AGS or MKN 28 cells treated with wild-type H. pylori. In conclusion, our study shows increased cPLA2 expression and PLA2activity in the gastric mucosae of patients with H. pyloriinfection and no change in epithelial cell lines exposed to H. pylori.

scholarly journals Pseudomonas aeruginosa Gene Products PilT and PilU Are Required for Cytotoxicity In Vitro and Virulence in a Mouse Model of Acute Pneumonia

1999 ◽  
Vol 67 (7) ◽  
pp. 3625-3630 ◽  
Author(s):  
James C. Comolli ◽  
Alan R. Hauser ◽  
Leslie Waite ◽  
Cynthia B. Whitchurch ◽  
John S. Mattick ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cell ◽  
Mouse Model ◽  
Cell Lines ◽  
Twitching Motility ◽  
Wild Type ◽  
Epithelial Cell Lines ◽  
Acute Pneumonia

ABSTRACT Type IV pili of the opportunistic pathogen Pseudomonas aeruginosa mediate twitching motility and act as receptors for bacteriophage infection. They are also important bacterial adhesins, and nonpiliated mutants of P. aeruginosa have been shown to cause less epithelial cell damage in vitro and have decreased virulence in animal models. This finding raises the question as to whether the reduction in cytotoxicity and virulence of nonpiliated P. aeruginosa mutants are primarily due to defects in cell adhesion or loss of twitching motility, or both. This work describes the role of PilT and PilU, putative nucleotide-binding proteins involved in pili function, in mediating epithelial cell injury in vitro and virulence in vivo. Mutants of pilT and pilU retain surface pili but have lost twitching motility. In three different epithelial cell lines, pilT or pilU mutants of the strain PAK caused less cytotoxicity than the wild-type strain but more than isogenic, nonpiliated pilA or rpoN mutants. ThepilT and pilU mutants also showed reduced association with these same epithelial cell lines compared both to the wild type, and surprisingly, to a pilA mutant. In a mouse model of acute pneumonia, the pilT and pilUmutants showed decreased colonization of the liver but not of the lung relative to the parental strain, though they exhibited no change in the ability to cause mortality. These results demonstrate that pilus function mediated by PilT and PilU is required for in vitro adherence and cytotoxicity toward epithelial cells and is important in virulence in vivo.

Bcl-2 protein localizes to the chromosomes of mitotic nuclei and is correlated with the cell cycle in cultured epithelial cell lines

1994 ◽  
Vol 107 (2) ◽  
pp. 363-371
Author(s):  
Q.L. Lu ◽  
A.M. Hanby ◽  
M.A. Nasser Hajibagheri ◽  
S.E. Gschmeissner ◽  
P.J. Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Lines ◽  
Cytoplasmic Localization ◽  
Human Epithelial Cell ◽  
Daughter Cells ◽  
Epithelial Cell Lines ◽  
Cell Immortalization

bcl-2 gene expression confers a survival advantage by preventing cells from entering apoptosis. In contrast to the previously described cytoplasmic localization of Bcl-2 in epithelial cells in vivo, in this study we have demonstrated, in a series of human epithelial cell lines, that Bcl-2 also localizes to mitotic nuclei. Both immunocytochemical and immunoelectron microscopical examinations localize this protein to nuclei and in particular to chromosomes. Nuclear Bcl-2 expression in these cell lines is correlated with the cell cycle. There is relatively strong expression during mitosis, most intense during prophase and metaphase, declining in telophase and then the protein becomes undetectable soon after separation of the two daughter cells. The expression and distribution of Bcl-2 is influenced by treatment with excessive thymidine. These results indicate that Bcl-2 may protect the cells from apoptosis occurring during mitosis and suggest a possible role for the protein in cell immortalization.

scholarly journals Comparing various epithelial cell lines as in vitro models for Francisella tularensis non‐phagocytic infections

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Karen Y Lo ◽  
Michael D Chua ◽  
Salima Abdulla ◽  
HT Law ◽  
Julian A Guttman
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Francisella Tularensis ◽  
In Vitro Models ◽  
Epithelial Cell Lines

Cytokine-mediated PGE2expression in human colonic fibroblasts

1998 ◽  
Vol 275 (4) ◽  
pp. C988-C994 ◽  
Author(s):  
Edward C. Kim ◽  
Yingting Zhu ◽  
Valerie Andersen ◽  
Daniela Sciaky ◽  
H. James Cao ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Shape Change ◽  
Cell Types ◽  
Mrna Levels ◽  
Primary Fibroblast ◽  
Fibroblast Cultures ◽  
Epithelial Cell Lines ◽  
Factor Α

We investigated prostanoid biogenesis in human colonic fibroblasts (CCD-18Co and 5 primary fibroblast cultures) and epithelial cell lines (NCM460, T84, HT-29, and LS 174T) and the effect of PGE2 on fibroblast morphology. Cytokine-stimulated PGE2production was measured. PGH synthase-1 and -2 (PGHS-1 and -2) protein and mRNA expression were evaluated. Basal PGE2 levels were low in all cell types (0.15–6.47 ng/mg protein). Treatment for 24 h with interleukin-1β (IL-1β; 10 ng/ml) or tumor necrosis factor-α (50 ng/ml), respectively, elicited maximal 25- and 6-fold inductions of PGE2 synthesis in CCD-18Co cultures and similar results in primary fibroblast cultures; maximal inductions with IL-1β in colonic epithelial cell lines were from zero to fivefold. Treatment of CCD-18Co fibroblasts with IL-1β caused maximal 21- and 53-fold increases, respectively, in PGHS-2 protein and mRNA levels without altering PGHS-1 expression. PGE2 (0.1 μmol/l) elicited a dramatic shape change in selected fibroblasts. Colonic fibroblasts are potentially important as cytokine targets and a source of and target for colonic prostanoids in vivo.

Sign in / Sign up

Export Citation Format

Share Document