Changes In Cell Kinetics Research Articles

Wound healing in aged skin exhibits systems-level alterations in cellular composition and cell-cell communication.

Delayed and often impaired wound healing in the elderly presents major medical and socioeconomic challenges. A comprehensive understanding of the cellular/molecular changes that shape complex cell-cell communications in aged skin wounds is lacking. Here, we use single-cell RNA sequencing to define the epithelial, fibroblast, immune cell types, and encompassing heterogeneities in young and aged skin during homeostasis and identify major changes in cell compositions, kinetics, and molecular profiles during wound healing. Our comparative study uncovers a more pronounced inflammatory phenotype in aged skin wounds, featuring neutrophil persistence and higher abundance of an inflammatory/glycolytic Arg1Hi macrophage subset that is more likely to signal to fibroblasts via interleukin (IL)-1 than in young counterparts. We predict systems-level differences in the number, strength, route, and signaling mediators of putative cell-cell communications in young and aged skin wounds. Our study exposes numerous cellular/molecular targets for functional interrogation and provides a hypothesis-generating resource for future wound healing studies.

Real-Time Study of Rapid Spread of Antibiotic Resistance Plasmid in Biofilm Using Microfluidics.

Gene transfer in biofilms is known to play an important role in antibiotic resistance dissemination. However, the process remains poorly understood. In this study, microfluidics with time-lapse imaging was used for real-time monitoring of plasmid-mediated horizontal gene transfer (HGT) in biofilms. Pseudomonas putida KT2440 harboring an antibiotic resistance plasmid RP4 was chosen as the donor while Escherichia coli and activated sludge bacteria were used as the recipient cells. Dynamic features of the transfer process, including the transfer rate, cell growth rate and kinetic changes of the transfer frequency, were determined. It was found that the routes for gene transfer strongly depend on the structure and composition of a biofilm. While intraspecies HGT is essential to initiate a transfer event, the secondary retransfer from transconjugants to the same species is more efficient and can cause cascading gene spread in single-strain biofilms. For the activated sludge biofilm, only small and scattered colonies formed and vertical gene transfer appears to be the dominant route after initial intraspecies transfer. Furthermore, more than 46% of genera in the activated sludge were permissive to plasmid RP4, many of which are associated with human pathogens. These phenomena imply early prevention and interruptions to biofilm structure could provide an effect way to inhibit rapid antibiotic resistance gene spread and reduce the likelihood of catastrophic events associated with antibiotic resistance.

Transcriptional upregulation of HIF-1α by NF-κB/p65 and its associations with β-catenin/p300 complexes in endometrial carcinoma cells

The hypoxia-inducible factor (HIF)-1α, which has a major role in cell adaptation to hypoxia, is mainly regulated at post-translational levels. Recently, HIF-1α mRNA was also shown to be upregulated by several signal pathways under normoxic conditions. Here we focused on relationships of HIF-1α with NF-κB and β-catenin signaling in endometrial carcinomas (Em Cas). Long-term exposure of Ishikawa cells to cobalt chloride (CoCl2), which is known to mimic the effect of hypoxia, caused a decrease in the growth, along with increased HIF-1α protein but not mRNA expression. In contrast, short-term exposure resulted in a rapid and transient increase in HIF-1α mRNA expression along with stabilization of nuclear NF-κB/p65 (p65). Transfection of p65 increased HIF-1α expression through activation of the promoter, whereas overexpression of HIF-1α also activated NF-κB-dependent transcription, indicating the existence of a positive feedback loop. In addition, HIF-1α was indirectly associated with nuclear β-catenin through interactions with p300, leading to slight enhancement of both HIF-1α- and β-catenin-mediated transcriptional activity. In clinical samples, biphasic upregulation of HIF-1α expression was observed in normal endometrial glandular components during the menstrual cycle, with the labeling indices showing significantly higher values in the early secretory stage. Significantly higher values for phosphorylated p65 and nuclear β-catenin were also observed in HIF-1α-positive than -negative lesions of Em Cas, in contrast to significantly lower Ki-67 status. These data therefore suggest that transcriptional associations with HIF-1α and NF-κB, as well as β-catenin/p300 complexes, may contribute to modulation of changes in tumor cell kinetics in response to a hypoxic condition in Em Cas.

Irinotecan‐induced alterations in intestinal cell kinetics and extracellular matrix component expression in the dark agouti rat

Chemotherapy-induced mucositis is characterized by damage of mucous membranes throughout the alimentary tract (AT). Extracellular matrix (ECM) components play a vital role in maintaining mucosal barrier integrity by regulating cellular apoptosis, proliferation and differentiation of overlying epithelial cells. The aims of this study were to characterize the changes in epithelial cell kinetics and to investigate the expression of the ECM components in the gastrointestinal tract following irinotecan administration. Female dark agouti rats were treated with single 200 mg/kg dose irinotecan and killed at various time points (1, 6, 24, 48, 72, 96 and 14 h) after treatment. Ki67 immunostaining and TUNEL were used to assess proliferation and apoptosis, respectively, in the jejunum and colon. Masson trichrome staining and picro-sirius red staining were used to determine the level of collagen, and immunohistochemistry was used to further assess collagen IV, fibronectin and laminin 1 and 2 expression in these tissues. Irinotecan halved cellular proliferation in the jejunum and colon at 48 and 24 h, respectively, while apoptosis peaked at 6 h (P < 0.05). There was a substantial increase in total collagen deposits around crypts from 24 h in both regions. However, collagen IV expression decreased significantly in the crypt region in a delayed fashion (P < 0.05). Fibronectin expression decreased significantly in jejunum and colon from 6 to 24 h following treatment (P < 0.05). Irinotecan induced a significant alteration in epithelial cell kinetics in both the jejunum and colon, and this correlated with changes in ECM component expression. Changes in ECM expression may have a direct impact on the loss of mucosal layer integrity evident in chemotherapy-induced mucositis.

Life and death in the atherosclerotic plaque

Changes in cell mass in atherosclerosis represent changes in cell division, cell death and migration/emigration, all of which may be occurring simultaneously in different cell types at different times and in different regions of the plaque. This makes measurement of these individual processes and measurement of overall cell kinetics in atherosclerosis difficult, with the challenges and shortfalls only recently becoming apparent. This review will outline the problems associated with assaying cell proliferation and cell death, and how these processes relate to changes in overall cell kinetics and measurement of biological age. Cell division and cell death have historically been assayed as frequencies of specific processes, with at times ill-defined and nonspecific markers. More recent studies have moved towards cumulative assays that can measure overall rates over time, resulting in a 'biological' age or replication history of a tissue or cell. The complexity of processes involved in assaying changes in cell kinetics in atherosclerosis mean that we must move towards cumulative assays of cell proliferation, cell death and senescence that can be measured in the time frames over which atherosclerosis occurs, and for studies that selectively manipulate one of these processes in a single-cell type without affecting other processes.

Aging Epidermis Is Maintained by Changes in Transit-Amplifying Cell Kinetics, Not Stem Cell Kinetics

It has been assumed that the slow rate of healing in aging epidermis is due to slowing of the epidermal stem cell proliferative rate. In this issue, Charruyer et al. report that this may not be the case. Using a long-term repopulating model, they demonstrate that epidermal stem cell kinetics are maintained. Instead, it is the compensatory action of the transit-amplifying (TA) cells that changes in aging skin and thus bears responsibility for slowed wound healing.

Changes in endothelial cell kinetics after short-term rat gavage exposure to riddelliine—An hepatic endothelial carcinogen

Changes in endothelial cell kinetics after short-term rat gavage exposure to riddelliine—An hepatic endothelial carcinogen

Changes in endothelial cell kinetics after short-term rat gavage exposure to riddelliine—An hepatic endothelial carcinogen

Changes in endothelial cell kinetics after short-term rat gavage exposure to riddelliine—An hepatic endothelial carcinogen

Concurrent hormone and radiation therapy in patients with breast cancer: what is the rationale?

Endocrine therapy is often given together with postoperative radiotherapy in patients with breast cancer and positive hormone-receptor status. However, few experimental or clinical studies address the combined effects of hormone and radiation therapy. Preclinical models have shown changes in tumour cell kinetics with the addition of tamoxifen, and some show reduced tumour cell death with concurrent anti-oestrogen treatment and radiotherapy. Although data from in-vitro studies support the notion of antagonistic effects of concurrent tamoxifen and radiotherapy on tumour cells, in-vivo research suggests a synergistic effect that could be attributable to micro-environmental changes in tumour responsiveness to ionising radiation and hormone therapy. Retrospective studies suggest that in practical application, concurrent administration of tamoxifen with radiotherapy does not compromise local control but might increase toxicity. Preliminary results from simultaneous treatment with aromatase inhibitors and radiation indicate that this combination of endocrine and radiation therapy could enhance cytotoxicity and improve tumour response. Further studies are needed to clarify the physiological mechanisms activated by oestrogens, which will allow a more thorough understanding of the complex interactions between 17beta-oestradiol and P53/P21(WAF1/CIP1)/Rb pathways and of the interaction between endocrine therapy and radiotherapy.

Comments on the paper by E. M. Minicucci et al. “DNA damage in lymphocytes and buccal mucosa cells of children with malignant tumours undergoing chemotherapy”

I read the paper by Minicucci et al. ‘‘DNA damage in lymphocytes and buccal mucosa cells of children with malignant tumours undergoing chemotherapy’’ [1] with great interest because recently I analyzed all available literature sources concerning the influence of chemoand radiotherapies on exfoliated mucosal cells [2]. The problem of possible micronuclei (MN)-inducing activity of antiblastics on epithelial oral mucosa cells has not been studied well. Only four papers were published concerning cancer patients (for review see [2]) and two concerning patients with other diseases treated with cytostatics [3, 4]. It has been shown that in these papers positive effect was registered in some cases. But no firm conclusion could be drawn if chemotherapy induces MN in oral epithelial cells. I think it is because all investigators applied various time points to collect exfoliated epithelial cells after the application of cytostatics. For example, it is practically not clear when the samples of buccal cells were collected by Minicucci et al. [1]. The time factor could play a key role in finding of MN because of kinetics (or the life cycle) of these types of cells. According to Szete et al. [5], the half-life of buccal cells is about 15 days and Kassie et al. [6] showed that MN level is highest 28 days after the effect of mutagen. After that there is an elimination of cells with MN. Hence, collection of oral cells ought to be done not later than 30 days after the last application of cytostatic drug. In my opinion, success of such kind of investigations depends mainly on the study of primary patients (without any treatment which can induce damage of cytogenetic structures) after one cycle of chemotherapy because it is mostly toxic for organism, and it could induce changes in basal cell kinetics. Also, due to this the so-called nuclear anomalies (karyolysis, karyorrhexis, pycnosis) can appear [7]. The evaluation of the so-called nuclear anomalies along with MN will improve the quality of the studies. Minicucci et al. [1] found significantly increased levels of MN in lymphocytes which were collected at the same time as exfoliated cells. It is because, unlike epithelial cells, half-life of lymphocytes is substantially longer (some years) that it is possible to find an increased number of MN in lymphocytes of children under therapy of much longer time than 30 days (the critical time point to register MN in epithelial cells) [8]. It is noteworthy that Torres-Bugarin et al. [7] investigated about 40 patients under antiblastic therapy, and found significantly increased levels of MN in some of them. But among them were subjects after two or even three cycles of therapy. Like Minicucci et al. [1], no firm information was presented as to when the buccal cells were collected. Based on the data presented by the authors, the number of cells with MN only in primary cancer patients treated with three chemotherapeutic schedules was calculated. Totally among them 19 were primary, and MN frequencies were 1.6 ± 0.4% before and 2.6 ± 0.7% after treatment (p [ 0.05, Mann–Whitney test). In ten patients treated with carboplatin ?5-fluorouracil MN numbers were 0.95 ± 0.12% before and 1.35 ± 0.42% after treatment, and in nine patients treated with isophosphamide ? epirubicin the frequencies were 2.9 ± 1.0% (before) and 4.9 ± 1.6% (after treatment) (p [ 0.05 in both cases, Mann–Whitney U test). As can be noted, no significant increase of cells with MN was found also in primary patients after one course of therapy. But the time of cell collection was not clearly indicated by the authors [1]. Ramos-Remus studied and A. Nersesyan (&) Institute of Cancer Research, Vienna, Austria e-mail: armen.nersesyan@meduniwien.ac.at

Mucosal morphology, cell proliferation and faecal bacteriology in acute pouchitis.

A study was performed to investigate whether acute reservoir ileitis (pouchitis) is associated with specific changes in mucosal morphology, crypt cell kinetics and faecal bacteriology in the ileal pouch. Forty-six patients were studied (ileal reservoir, 36; end ileostomy, ten) using clinical grading, sigmoidoscopy and biopsy; 24 patients with a reservoir were restudied after therapy for 1 month with metronidazole 400 mg three times daily. An index of villus atrophy and crypt cell production rate (CCPR) were determined in all biopsy material. Faecal bacteriology was assessed in 12 patients with a pouch before and after metronidazole therapy. The mucosa of patients with pouchitis was associated with a lower villus atrophy index (P = 0.052), a higher CCPR (P = 0.03) and a higher grade of acute inflammation than that in those without pouchitis. There was no difference in faecal bacterial counts between patients with and without pouchitis. A low atrophy index correlated with a high CCPR (P < 0.001), worse functional score (P < 0.001) and more severe pouch mucosal acute inflammation (P < 0.001), but not with faecal bacteriology. Following metronidazole therapy there was resolution of acute pouch inflammation, increased villus atrophy index (P = 0.049), decreased CCPR (P = 0.049) but no differences in faecal bacterial counts apart from Bacteroides species. These data show that metronidazole therapy does not specifically alter the growth of common faecal bacteria in patients with pouchitis, apart from Bacteroides species. However, metronidazole causes resolution of the typical changes in pouch mucosal morphology and crypt cell kinetics associated with pouchitis.

Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: Implications on chemoprevention

Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group. This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg.d)) or indomethacin (3 mg/(kg.d)) to gain more insights into the chemopreventive mechanism. The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining. Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P<0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P<0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg.d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development. Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression.

Potentiation of 5-fluorouracil efficacy. Molecular mechanisms playing a role in the cytotoxic action of 5-fluorouracil and 5-ethyl-2'-deoxyuridine (EUdR) combination

Pharmacologic modulation of 5-fluorouracil (5-FU) metabolism provides a possibility for the enhancement of its clinical efficacy. The purpose of the present work was to study the effect of 5-ethyl-2'-deoxyuridine (EUdR), a potent 5-FU modulator, on different molecular mechanisms, influenced by 5-FU itself, and to obtain further data about the mode of action of the combination. SW620 cell line was used for the experiments. Cytotoxicity was studied by MTT test, cell kinetic changes by FACStar flow cytometer, apoptosis by fluorescent microscope after staining the cells with acridine orange and ethydium bromide, DNA fragmentation by PAGE electrophoresis after RNase and proteinase-K digestion, thymidine incorporation with 3H-thymidine, p53 and PCNA protein expression by Western blotting. The cytotoxicity of 5-FU was potentiated dose dependently by EUdR. One hundred muM concentration of EUdR resulted in a 40% decrease of the IC50 value of 5-FU. Cell cycle arrest in the G2/M transition phase was most pronounced after combined treatment with 5-FU+EUdR. EUdR potentiated the incorporation of 3Hthymidine into DNA. In addition to the increase of apoptosis rate, the expression of p53 protein, caused by 5-FU was further potentiated by UdR. This study demonstrated a potential novel approach to increase the efficacy of 5-FU by EUdR, which incorporated two complementary molecular actions, the selective modulation of TS inhibition and potentiation of the p53 protein expression, consequently leading to an increase in the apoptotic rate.

Keratinocyte stem cells, label-retaining cells and possible genome protection mechanisms.

Stem cells are the crucial cells upon which the entire tissue is dependent. Here we define and discuss what is meant by and known about keratinocyte stem cells. One way in which these cells have been studied is by their ability to retain radioactivity labelled thymidine for long periods of time (label retaining cells, LRCs). The underlying mechanism has been assumed in the past to be slow cycling but a more likely explanation is the selective segregation of old and new DNA strands (Cairns's hypothesis). Experiments in the small intestine indicate that the stem cells here are selectively sorting their DNA and becoming LRCs. A possible role for p53 in stem cell biology is presented.

Sister chromatid exchange induction by the herbicide 2,4-dichlorophenoxyacetic acid in chick embryos

As genetic damage may result from exposure to agricultural chemicals, it seemed appropriate to assess the genotoxic potential of 2,4-dichlorophenoxyacetic acid (2,4-D), a widely used broad-leaf herbicide, using a test system that may provide some indications on the genetic risk to animal species in the wild. In the present study, sister chromatid exchange (SCE) induction and cell cycle kinetics alterations by 2,4-D in 4-day old chick embryos were evaluated. Both a commercial herbicide formulation containing 37% 2,4-D isooctyl ester as active ingredient and pure 2,4-D were tested. Chick embryos were treated with 0, 0.5, 1, 2, or 4 mg 2,4-D. Test solutions were applied to the inner shell membrane on day 0 of incubation. Either commercial formulation or pure 2,4-D induced a dose-related increase in SCE frequency over the concentration range from 0 to 4 mg/embryo. Significantly higher SCE frequency was seen for the 4-mg group of embryos treated with the commercial product. A slightly higher SCE value was observed for the vehicle group (acetone-treated embryos) compared with the negative controls (untreated embryos). Significant inhibition of cell cycle progression was evident in both experimental groups and was generally dose related. The extent of changes in cell kinetics was similar in both groups, although somewhat more marked in the group treated with pure 2,4-D. The present findings corroborate the positive results from recent in vivo rodent studies.

Cell kinetic changes in human squamous cell carcinomas during radiotherapy studied using the in vivo administration of two halogenated pyrimidines

The aim of this study was to investigate cell cycle changes during radiation treatment and establish whether treatment intervention could be considered if these changes helped to predict outcome. 33 patients with head and neck cancer were administered iododeoxyuridine (IdUrd) prior to treatment and a second administration of bromodeoxyuridine (BrdUrd) prior to the fifth fraction of 2 Gy. Biopsies were taken several hours after each injection and flow cytometry was used to calculate changes in the cellular kinetics and cell cycle delay in vivo. The kinetic response of the tumour cells was variable; some showed an increase in proliferation during the first week of treatment, whilst the majority showed an inhibition of proliferation. Reduction in the labelling index (LI) and the pretreatment DNA ploidy status and not delays in G2 were the only parameters to correlate with clinical outcome. A lack of reduction in the LI after 1 week of radiotherapy and DNA aneuploidy predicted a group of patients where radiotherapy failed. This information could be helpful in planning future treatment interventions.

Loss of DCC expression in astrocytomas: relation to p53 abnormalities, cell kinetics, and survival.

Although frequent reduction or loss of DCC (deleted in colorectal carcinomas) has been demonstrated in gliomas, the association with cell kinetics and survival is still unclear. A total of 119 astrocytomas, comprising 39 grade IV, 36 grade III, and 44 low grade tumours, were immunohistochemically investigated, along with 26 normal adult brain samples and two fetal brains. The results were compared with p53 abnormalities, Ki-67 labelling index (LI), mitotic index (MI), apoptotic index (AI), and survival. In normal adult and fetal brain tissues, DCC expression was detected in mature and terminally differentiated neuronal cells but not glial elements. In astrocytomas, whereas DCC expression was still clearly shown with low grade malignancy, DCC scores were significantly decreased in high histological grade malignancy, along with an increase in cell kinetics determined by AI, MI, and Ki-67 LI values. In addition, p53 LI values were significantly increased, although a direct link between DCC scores and p53 LI values was not evident. Univariate analysis revealed that high DCC scores and low p53 LI values were closely related to a favourable outcome for astrocytoma, although only the AI was an independent prognostic factor. The loss of DCC expression may be closely related to changes in cell kinetics and tumour phenotype in astrocytomas, independent of p53 abnormalities.

Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines

Integration of chemotherapy and radiation is the standard practice in the management of locally advanced inoperable NSCLC. To assess the biological interaction between third generation chemotherapeutic agents and radiation in non-small cell lung cancer (NSCLC) in vitro, we tested a number of different drugs (paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cisplatin) combined with radiation, in lung cancer cell lines. Cellular chemosensitivity was determined, using the semi-automated colorimetric MTT assay, after 48, 72 and 96 h of exposure to increasing drug concentrations, (0.001–100 μM) and radiation doses (100–400 cGy). Cell lines used were the adenocarcinoma (ADK), A-549, and the squamous-cell carcinoma (SCC), LX-1. Cells were pre-treated with anticancer agents at 24, 12 and 0 h before irradiation. Cytofluorimetric cell cycle analysis was performed. A significant S-phase block or a G 2/M block was seen with gemcitabine and topotecan or paclitaxel pre-treatment, respectively. Apoptosis was seen only after paclitaxel exposure in the A-549 cell line. Despite a similar pattern of cell–kinetic changes induced by chemotherapy pre-treatment in all cell lines, the adenocarcinoma A-549 cell line was not radiosensitized by any of the anticancer agents tested, whereas synergism was observed in the LX-1 squamous carcinoma cell line, when exposed to gemcitabine, SN-38, topotecan and cisplatin. Paclitaxel, despite a favourable cell cycle effect, was not found to be synergistic with radiotherapy in our experimental model. In conclusion, the observed synergism appears to be dose- and timing-independent and seems to be related to the histological subtype being present in SCC only. Favourable perturbation of the cell cycle is evident with all the new agents tested in both cell types, but was not sufficient to produce synergism with radiation.

Interleukin-1, interleukin-8, tumour necrosis factor alpha and interferon gamma stimulate DNA synthesis but have no effect on apoptosis in small-intestinal cell lines.

Cytokines stimulate lymphocyte cell proliferation and affect cell division in several other cell types. Helicobacter pylori-induced gastritis and coeliac disease are characterized by an increased cell proliferation in association with an increased production of proinflammatory cytokines, which could contribute to these cell kinetic changes. Our aim is to examine in vitro whether cytokines usually present in the gastrointestinal mucosa affect DNA synthesis and apoptosis in a rat and a human small-intestinal cell line. IEC-6 and FHs-74 cells were incubated for 24 h with 10(-13)-10(-9) M of tumour necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor-beta (TGF-beta) and interferon gamma (IFN-gamma). IEC-6 cells were also incubated with 10(-13)-10(-9) M of interleukin-1alpha (IL-1alpha) and 10(-8) M of interleukin-1 receptor antagonist (IL-1ra). The cells were labelled with 3H-methyl thymidine for the final 4 hours, and then processed for autoradiography. DNA synthesis was evaluated by the labelling index (LI%). Apoptosis was evaluated in IEC-6 cells by changes in membrane lipid asymmetry using annexin-V binding to externalized phosphatidylserine (flow cytometry) and by estimating the caspase activity. TNF-alpha, IL-1beta, IL-8 and IFN-gamma significantly and markedly increased the LI, even at low concentrations (P< 0.0001), in both IEC-6 and FHs-74 cells, as did IL-1alpha in IEC-6 cells. TGF-beta significantly reduced the LI in both cell lines (P< 0.0001), whereas IL-2, IL-6 and IL-1ra did not affect DNA synthesis significantly. None of IL-1beta, IL-8, TNF-alpha or IFN-gamma affected apoptosis in IEC-6 cells. TNF-alpha, IL-1alpha, IL-1beta, IL-8 and IFN-gamma stimulated DNA synthesis in a human and a rat small-intestinal cell line. The cytokines exert their mitogenic action directly on the intestinal cells via specific receptors. Our findings indicate that pro-inflammatory cytokines may participate in the regulation of the gastrointestinal epithelial cell proliferation in health and disease.

Changes in cell kinetics of gastric intestinal metaplasia before and after Helicobacter pylori eradication

Changes in cell kinetics of gastric intestinal metaplasia before and after Helicobacter pylori eradication