Inhibition of mucin release from airway goblet cells by polycationic peptides

1999 ◽  
Vol 277 (4) ◽  
pp. L811-L815 ◽  
Author(s):  
Kwang Ho Ko ◽  
Choong Jae Lee ◽  
Chan Young Shin ◽  
Mijeong Jo ◽  
K. Chul Kim
Keyword(s):  
Lactate Dehydrogenase ◽  
Epithelial Cells ◽  
Goblet Cells ◽  
Inhibitory Effect ◽  
Treatment Groups ◽  
Lactate Dehydrogenase Release ◽  
Significant Difference ◽  
Dose Dependent Fashion ◽  
Mucin Release ◽  
Dose Dependent

In the present study, we investigated whether polycationic peptides affect mucin release from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled with [3H]glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of either poly-l-arginine (PLA) or poly-l-lysine (PLL) to assess the effects on [3H]mucin release. Possible cytotoxicity by the polycations was assessed by measuring lactate dehydrogenase release,51Cr release, and cell exfoliation. The results were as follows: 1) both PLA and PLL inhibited mucin release in a dose-dependent fashion; 2) there was no significant difference in either lactate dehydrogenase release,51Cr release, or the number of floating cells between control and treatment groups; 3) the effects of both PLA and PLL on mucin release were completely blocked by neutralizing the positive charges either by pretreatment with heparin or by N-acetylation of the polycations; and 4) both PLA and PLL completely masked the stimulatory effect of ATP on mucin release. We conclude that these polycationic peptides can inhibit mucin release from airway goblet cells without any apparent cytotoxicity, and the inhibitory effect seems to be attributable to their positive charges. These are the first nonsteroidal agents, to the best of our knowledge, that have been shown to inhibit mucin release from airway goblet cells.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

Dexamethasone and 8-bromo-cyclic AMP depress the incorporation of [3H]thymidine into mouse condylar cartilage by different pathways

1986 ◽  
Vol 109 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Z. Kraiem ◽  
G. Maor ◽  
M. Silbermann
Keyword(s):  
Cyclic Amp ◽  
Thymidine Incorporation ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Condylar Cartilage ◽  
Camp Analogue ◽  
Dose Dependent Fashion ◽  
Cartilage Cells ◽  
Dose Dependent

ABSTRACT We examined whether cyclic AMP (cAMP) affects the incorporation of [3H]thymidine into cartilage cells and, if so, whether this action could be related to the inhibitory effect of glucocorticoid hormones on the growth of ossifying cartilage. Incorporation of [3H]thymidine into trichloroacetic acid-precipitable material by mouse cartilage was measured concomitantly with the concentration of cAMP. Dexamethasone (1 μmol/l) significantly (P < 0·05) depressed the incorporation of [3H]thymidine. The cAMP analogue 8-bromo-cAMP (0·01–1 mmol/l) also depressed the incorporation of the radionucleotide in a dose-dependent fashion. When various concentrations of 8-bromo-cAMP were added with dexamethasone (1 μmol/l), no apparent changes took place compared with the effect of dexamethasone alone. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0·2-1 mmol/l) elicited an inhibitory effect on [3H]thymidine incorporation and a stimulatory influence on cartilage cAMP concentrations. Dexamethasone, at doses (0·01–1 μmol/l) causing significant inhibition of [3H]thymidine incorporation, failed to increase cartilage levels of cAMP. It seems, therefore, that the depressive effect of dexamethasone on [3H]thymidine incorporation in condylar cartilage is not mediated through an increase of cAMP in the tissue. J. Endocr. (1986) 109, 209–213

The effects of ozone exposure on lactate dehydrogenase release from human and primate respiratory epithelial cells

1994 ◽  
Vol 70 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Karen Dumler ◽  
Quentin S. Hanley ◽  
Coralie Baker ◽  
Daniel L. Luchtel ◽  
Leonard C. Altman ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Epithelial Cells ◽  
Ozone Exposure ◽  
Respiratory Epithelial Cells ◽  
Lactate Dehydrogenase Release ◽  
Respiratory Epithelial

Density and distribution of feline conjunctival goblet cells

2016 ◽  
Vol 19 (10) ◽  
pp. 1048-1054 ◽  
Author(s):  
Réka Eördögh ◽  
Csaba Jakab ◽  
Renáta Papp ◽  
Alexander Tichy ◽  
Barbara Nell
Keyword(s):  
Epithelial Cells ◽  
Periodic Acid ◽  
Goblet Cells ◽  
Lower Eyelid ◽  
Bulbar Conjunctiva ◽  
Temporal Region ◽  
The Third ◽  
Significant Difference ◽  
Effect Of Age ◽  
Age And Sex

Objectives The objective of this study was to examine the density and distribution of goblet cells (GCs) in the feline conjunctiva and to investigate a potential effect of age and sex on GC density (GCD). Methods Thirty-nine eyes of 21 cats euthanased for reasons unrelated to this study were used. Fixed upper and lower eyelid and bulbar conjunctiva were divided into nasal and temporal regions. The third eyelid was excised and investigated separately. Samples were embedded in paraffin wax; sections were stained with periodic acid–Schiff reaction and analysed with light microscopy. To determine the topographic distribution of GCs, each region was subdivided into the marginal, palpebral and bulbar zone. In each zone 200 epithelial cells, including GCs, were counted. Goblet cell index was defined as a percentage of the epithelial cells. Results The palpebral zone of both eyelids contained significantly ( P <0.001) more GCs (27.5–32.0%) than the marginal or bulbar areas. The highest GCD was found in the nasal palpebral zone of the upper eyelid (32.0%). Marginal and bulbar sites contained fewer numbers of GCs (2.6–10.0%). The lowest GCD was detected in the nasal bulbar zone of the lower eyelid (2.6%). Overall the nasal region contained significantly ( P = 0.036) more GCs than the temporal region, but there was no significant difference in GCD between the upper and lower eyelids. Correlation analysis did not show any effect of age or sex on GC counts. Conclusions and relevance GCD in the palpebral zones and on the anterior surface of the third eyelid was highest; the lowest density was found in the bulbar zones of the lower eyelid and in the marginal zones of both eyelids. Overall, higher GCD was found in the cat than in other species. Age and sex have no effect on GCD.

scholarly journals Curcumin prevents renal oxidative stress and tissue damage induced by renal ischemia/reperfusion in rats

2018 ◽  
Vol 5 (10) ◽  
pp. 3192
Author(s):  
Nazile Erturk ◽  
Hulya Elbe ◽  
Zumrut Dogan ◽  
Serdar Aktas ◽  
Savas Demirbilek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Tissue ◽  
Renal Ischemia ◽  
Normal Morphology ◽  
Treatment Groups ◽  
Significant Difference ◽  
Intraperitoneal Dose ◽  
Dose Dependent

Background: There is increasing evidence to suggest that curcumin has antioxidant efficacy in renal ischemia reperfusion injury (IRI). However, it has not been investigated whether this effect is dose-dependent or not.  The aim of this study is to investigate the dose-dependent effect of curcumin on renal IRI in an experimental rat model.Methods: The rats (n=32) were separated into four groups: sham, I/R, I/R+CUR-50, I/R+CUR-100. Rats were subjected to renal ischemia by clamping bilateral renal pedicles for 60 min, and then reperfused for 3 h. Animals in treatment groups received 50 mg/kg/day and 100 mg/kg/day curcumin orally for 5 days before IRI, respectively. MDA, GSH, SOD, and CAT activities were determined in renal tissue. Renal tissue also evaluated histopathologically for mean histopathological damage score.Results: The mean MDA levels in the I/R+CUR-50 and I/R+CUR-100 groups were significantly decreased when compared with the I/R group (p=0.038 and p=0.016, respectively). SOD, CAT and GSH levels of all treatment groups were significantly increased in comparison to that of I/R group (p<0.05, for all). No statistically significant difference between treatment groups were detected (p>0.05). In histological examination, the rats treated with curcumin had nearly normal morphology of the kidney.Conclusions: Curcumin significantly ameliorates the damage of renal IRI by its antioxidant activity. We detected the highest intraperitoneal dose of curcumin reduced the IRI induced oxidative stress as 50 mg/kg per day.

scholarly journals Zebrafish as a model for haloperidol-induced catalepsy-like immobilization

2021 ◽  
Author(s):  
Akihiro Hasumi ◽  
Hideyuki Maeda ◽  
Ken-ichi Yoshida
Keyword(s):  
Drug Exposure ◽  
Inhibitory Effect ◽  
Suitable Model ◽  
Typical Antipsychotic ◽  
Activity Levels ◽  
Treatment Groups ◽  
Abnormal Movements ◽  
Bar Test ◽  
Dose Dependent ◽  
Increased Activity

Abstract This study investigated the validity of screening for antipsychotic-induced catalepsy-like immobilization in zebrafish (Danio rerio), as an alternative to the standard rodent model. To induce the desired symptoms, we used haloperidol, a typical antipsychotic that disturbs dopamine D2-receptors. In addition to observing swimming behaviors generally, we used the light and dark test to assess how drug exposure influences locomotive responses to those stimuli. We selected this test instead of the commonly used bar test for catalepsy in rodents, because fish cannot perform the necessary motions to participate in the latter. Normally, light attenuated activity and decreased locomotion, whereas darkness greatly increased activity levels in zebrafish. We confirmed that haloperidol had a dose-dependent inhibitory effect on activity; the highest dose of 10 mg/L almost stopped fish activity even in darkness. We did not observe any significant differences in heart rate or morphology across the control and treatment groups, whereas abnormal movements like rigid and erratic behaviors occurred in haloperidol-treated groups. Therefore, we found that immobilization and abnormal movements qualify as haloperidol-induced catalepsy. In conclusion, zebrafish appear to be a suitable model for antipsychotic-induced catalepsy-like immobilization.

l-Histidine decarboxylase decreases its own transcription through downregulation of ERK activity

2001 ◽  
Vol 281 (4) ◽  
pp. G1081-G1091 ◽  
Author(s):  
Rocchina Colucci ◽  
John V. Fleming ◽  
Ramnik Xavier ◽  
Timothy C. Wang
Keyword(s):  
Histidine Decarboxylase ◽  
Histamine Receptor ◽  
Inhibitory Effect ◽  
Protein Levels ◽  
Amino Terminal ◽  
Histamine Production ◽  
Extracellular Signal ◽  
Dose Dependent Fashion ◽  
Erk Activity ◽  
Dose Dependent

A poorly defined negative feedback loop decreases transcription of thel-histidine decarboxylase (HDC) gene. To help understand this regulation, we have studied the effect of HDC protein expression on HDC gene transcription in transfected AGS-B cells. Expression of the rat HDC protein inhibited HDC promoter activity in a dose-dependent fashion. The region of the HDC promoter mediating this inhibitory effect corresponded to a previously defined gastrin and extracellular signal-related kinase (ERK)-1 response element. Overexpression of the HDC protein reduced nuclear factor binding in this region. Experiments employing specific histamine receptor agonists indicated that the inhibitory effect was not dependent on histamine production, and studies with the HDC inhibitor α-fluoromethylhistidine revealed that inhibition was unrelated to enzyme activity. Instead, an enzymatically inactive region at the amino terminal of the HDC enzyme (residues 1–271) was shown to mediate inhibition. Fluorescent chimeras containing this domain were not targeted to the nucleus, arguing against specific inhibition of the HDC transcription machinery. Instead, we found that overexpression of HDC protein decreased ERK protein levels and ERK activity and that the inhibitory effect of HDC protein could be overcome by overexpression of ERK1. These data suggest a novel feedback-inhibitory role for amino terminal sequences of the HDC protein.

scholarly journals The Increased Expression of HLA-DR and ICAM-1 Molecules by Human Bronchial Epithelial Cells, Induced by Activated Mononuclear Cells, is Downregulated by Nedocromil Sodium

1994 ◽  
Vol 3 (7) ◽  
pp. S7-S13 ◽  
Author(s):  
O. Sacco ◽  
S. Lantero ◽  
L. Scarso ◽  
V. Frangova ◽  
V. Ottolini ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mononuclear Cell ◽  
Mononuclear Cells ◽  
Inhibitory Effect ◽  
Bronchial Epithelial Cells ◽  
Nedocromil Sodium ◽  
Bronchial Epithelial ◽  
Hla Dr ◽  
Ifn Γ ◽  
Dose Dependent

To test the hypothesis that mononuclear cell products could increase the expression of HLA-DR and ICAM-1 molecules in bronchial epithelial cells (BECs), subconfluent cultures of human BECs, obtained from surgically resected bronchi, were incubated with PHA-activated blood mononuclear cell conditioned media (BCM-CM) or recombinant IFN-γ. The presence of HLA-DR and ICAM-1 molecules on BECs was then evaluated by specific antibody staining and flow-cytometry analysis. The addition to BEC cultures of different concentrations of PHA-stimulated BMC-CM, or of IFN-γ induced a dosedependent increase of HIA-DR and ICAM-1 expression, while no effect was observed with unstimulated BMC-CM. The ability of nedocromil sodium and, as control, of dexamethasone, to prevent the upregulation of HLA-DR and ICAM-1 expression on BECs was then tested. Increasing concentrations (10−7to 10−4M) of nedocromil significandy inhibited HLA-DR and ICAM-1 expression by BECs in a dose-dependent fashion. A similarly dose-dependent inhibitory effect was also observed with dexamethasone, which, however, was less active than nedocromil on HL-ADR expression and more active on ICAM-1 expression. Finally, nedocromil and dexamethasone showed a significant synergistic effect on the expression of both cell surface molecules at the lowest concentrations tested.

Concurrent Spinal Infusion of MK801 Blocks Spinal Tolerance and Dependence Induced by Chronic Intrathecal Morphine in the Rat

1996 ◽  
Vol 84 (5) ◽  
pp. 1177-1188 ◽  
Author(s):  
Stuart Dunbar ◽  
Tony L. Yaksh
Keyword(s):  
Intrathecal Morphine ◽  
Receptor Activation ◽  
Acute Administration ◽  
Response Curves ◽  
Aspartate Receptor ◽  
Abnormal Posture ◽  
Significant Difference ◽  
Dose Dependent Fashion ◽  
20 Nm ◽  
Dose Dependent

Background MK801, an N-methyl-D-aspartate receptor antagonist, has recently been reported to attenuate tolerance to, and withdrawal from morphine. This study analyzes tolerance and withdrawal in a chronic intrathecal coinfusion model of morphine and MK801. Methods Intrathecal catheters, attached to 7-day miniosmotic infusion pumps, were implanted in rats and infused with saline, 20 nM/h morphine, MK801 (10 and 3 nM/h) + morphine; and 10 nM/h MK801. Analgesia was measured on the hot plate daily. On the day 7, groups received 3 mg/kg intraperitoneal naloxone and six signs of withdrawal were assessed: vocalization to air motion or light touch, abnormal posture, spontaneous vocalization, escape attempts, "wet dog shakes," and ejaculation. Similar groups were tested only on days 1 and 7. Intrathecal morphine dose-response curves were obtained on day 8. A separate morphine-tolerant group received 10 nM MK801 on day 7. Rats from each group received 10 nM intrathecal morphine 1 week later. Results Coinfusion of MK801 with morphine resulted in a dose-dependent preservation of effect, and attenuated three of six signs of withdrawal. Coinfusion of MK801 (10 and 3 nM/h) prevented the reduction of potency observed with morphine alone. ED50 values (maximum percent effect, nM morphine) were: saline (16), morphine (496), MK801 (10 nM/h) + morphine (4), and 10 nM/h MK801 (0.3). Acute administration of MK801 was ineffective in restoring sensitivity to morphine. One week after cessation of infusion, there was no significant difference between groups. Conclusions Chronic spinal MK801 attenuates tolerance to, and withdrawal from spinal morphine in a dose-dependent fashion, supporting the hypothesis that N-methyl-D-aspartate receptor activity plays a role in the reorganization of spinal function produced by chronic opioid receptor activation. Chronic intrathecal MK801 appears to sensitize the spinal cord to intrathecal morphine.

Antagonism by theophylline of the adenosine receptor agonist 5′-N-ethykarboxamidoadenosine at the guinea pig ileum

1985 ◽  
Vol 63 (9) ◽  
pp. 1195-1197 ◽  
Author(s):  
F. L. Christofi ◽  
M. A. Cook
Keyword(s):  
Guinea Pig ◽  
Receptor Agonist ◽  
Acetylcholine Release ◽  
Receptor Site ◽  
Inhibitory Effect ◽  
Guinea Pig Ileum ◽  
Competitive Antagonism ◽  
Adenosine Receptor Agonist ◽  
Dose Dependent Fashion ◽  
Dose Dependent

The inhibitory effect of the putative adenosine A2 receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) on acetylcholine release from the stimulated guinea pig ileum preparation and the nature of its antagonism by theophylline were investigated. NECA was shown to inhibit the response of the ileum preparation in a dose-dependent fashion, and an EC50 value of 1.62 × 10−8 M was determined. This value was comparable with that determined for the A1 receptor agonist N6-R-phenylisopropyladenosine (R-PIA) (2.57 × 10−8 M) using the same preparation. Competitive antagonism of the inhibitory effect of NECA by theophylline was quantitated and a pA2 value of 5.04 for the methylxanthine was obtained. This value was similar to those obtained previously for R-PIA and adenosine itself and suggests that these nucleosides may be interacting with the same receptor site on myenteric nerve endings. These findings do not permit the designation of the receptor as an A1 or A2 subtype according to current criteria.

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