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Biomedical subjects

J Mullol

Publications and source records attributed to J Mullol.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity.

BACKGROUND: Because little is known about micronutrient/antioxidant intake and asthma severity, we investigated dietary intake and plasma/serum levels of micronutrients/antioxidants in a group of asthma patients with various degrees of severity, and compared the results with healthy subjects. METHODS: A case control study was carried out on 118 asthma patients and 121 healthy subjects. The severity of the disease was classified by division of patients into four groups. Normal dietary micronutrient/antioxidant intake was estimated from a food frequency questionnaire. Plasma/serum levels of vitamins C, E, and A, selenium, magnesium, zinc, and platelet glutathione peroxidase (GSH-Px) activity were also determined. RESULTS: No differences in daily micronutrient/antioxidant intake were seen between patients and healthy subjects. The severity of the disease showed no significant relationship with micronutrient/antioxidant intake. There were no differences in plasma/serum levels in any of the micronutrients/antioxidants between healthy subjects and asthmatics. Nor were any differences found between asthma groups in severity in the biochemical measures, except in platelet GSH-Px activity, which was significantly lower in the most severe groups. CONCLUSIONS: In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.

Adolescent↗
PubMed2001

Effect of budesonide and nedocromil sodium on IL-6 and IL-8 release from human nasal mucosa and polyp epithelial cells.

We investigated the effect of budesonide and nedocromil sodium on the secretion of IL-6 and IL-8 by cultured epithelial cells from healthy nasal mucosa and nasal polyps. Human epithelial cell conditioned media was generated with fetal calf serum (FCS) in the presence or absence of budesonide and/or nedocromil sodium. Budesonide inhibited FCS-induced IL-6 and IL-8 release in a dose-dependent manner. The IC25 (25% inhibitory concentration) of budesonide on IL-6 release was higher in nasal polyp than in nasal mucosa epithelial cells (34 nM vs. 200 pM). The IC25 of budesonide on IL-8 release was higher in nasal mucosa than in nasal polyps (145 pM vs. 4 pM). Nedocromil sodium caused a dose-related inhibitory effect on IL-8 release from nasal mucosa (IC25, 207 nM), while it only had a significant effect in nasal polyps at 10(-5) M. Nedocromil sodium had no effect on IL-6 release. The inhibitory effect of budesonide was higher than that of nedocromil sodium on both nasal polyps and nasal mucosa. Budesonide and nedocromil sodium may exert their anti-inflammatory action in the respiratory mucosa by modulating the secretion of IL-6 and IL-8. The different effect of budesonide and nedocromil sodium on IL-6 and IL-8 release may be explained by differences in the mechanisms which regulate the upregulation of these cytokines in inflammatory responses.

Adolescent↗
PubMed2001

Proinflammatory cytokines and eosinophil cationic protein on glandular secretion from human nasal mucosa: regulation by corticosteroids.

BACKGROUND: Airway hypersecretion is a common finding in rhinitis and asthma in which proinflammatory cytokines are upregulated. The effect of inflammation on glandular secretion remains unclear. OBJECTIVE: We sought to investigate the effect of proinflammatory cytokines and eosinophil products in in vitro lactoferrin glandular secretion from human nasal mucosa and the role of corticosteroids and IL-10 in modulating this effect. METHODS: Nasal explants from patients undergoing turbinectomies were incubated in a controlled atmosphere (50% N(2), 5% CO(2), and 45% O(2)) at 37 degrees C. Nasal explants were incubated with or without IL-1beta, IL-4, IL-5, IL-8, eotaxin, GM-CSF, TNF-alpha, eosinophil cationic protein (ECP), IL-10, and budesonide in a time-course and dose-response fashion. Lactoferrin concentrations in culture supernatants were measured by means of ELISA. RESULTS: ECP (up to 30%) caused a dose-related stimulation of lactoferrin secretion. TNF-alpha (20 ng/mL) induced a significant increase of lactoferrin release from 8 hours (27.7% +/- 17.8%, P <.05) to 24 hours (40.8% +/- 17.2%, P <.01) compared with that found in media-treated explants. At 24 hours, TNF-alpha caused a dose-related stimulation of lactoferrin secretion (up to 35%). IL-1beta (65.3% +/- 15.2%, P <.05) and GM-CSF (15.7% +/- 6.7%, P <.05), both at 20 ng/mL, exerted a stimulatory effect only at 24 hours, and IL-4, IL-5, IL-8, and eotaxin had no significant effect. Budesonide caused a dose-related inhibition of lactoferrin secretion induced by IL-1beta (down to -76%) and TNF-alpha (down to -70%), whereas IL-10 had no effect. CONCLUSIONS: ECP and some proinflammatory cytokines (IL-1beta, TNF-alpha, and GM-CSF) may contribute to glandular hypersecretion in the inflamed nose. Corticosteroids may reduce nasal hypersecretion by blocking the direct effect of proinflammatory cytokines on glandular output.

Adult↗
PubMed2001

Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation.

Magnetic twisting cytometry (MTC) (Wang N, Butler JP, and Ingber DE, Science 260: 1124-1127, 1993) is a useful technique for probing cell micromechanics. The technique is based on twisting ligand-coated magnetic microbeads bound to membrane receptors and measuring the resulting bead rotation with a magnetometer. Owing to the low signal-to-noise ratio, however, the magnetic signal must be modulated, which is accomplished by spinning the sample at approximately 10 Hz. Present demodulation approaches limit the MTC range to frequencies <0.5 Hz. We propose a novel demodulation algorithm to expand the frequency range of MTC measurements to higher frequencies. The algorithm is based on coherent demodulation in the frequency domain, and its frequency range is limited only by the dynamic response of the magnetometer. Using the new algorithm, we measured the complex modulus of elasticity (G*) of cultured human bronchial epithelial cells (BEAS-2B) from 0.03 to 16 Hz. Cells were cultured in supplemented RPMI medium, and ferromagnetic beads (approximately 5 microm) coated with an RGD peptide were bound to the cell membrane. Both the storage (G', real part of G*) and loss (G", imaginary part of G*) moduli increased with frequency as omega(alpha) (2 pi x frequency) with alpha approximately equal to 1/4. The ratio G"/G' was approximately 0.5 and varied little with frequency. Thus the cells exhibited a predominantly elastic behavior with a weak power law of frequency and a nearly constant proportion of elastic vs. frictional stresses, implying that the mechanical behavior conformed to the so-called structural damping (or constant-phase) law (Maksym GN, Fabry B, Butler JP, Navajas D, Tschumperlin DJ, LaPorte JD, and Fredberg JJ, J Appl Physiol 89: 1619-1632, 2000). We conclude that frequency domain demodulation dramatically increases the frequency range that can be probed with MTC and reveals that the mechanics of these cells conforms to constant-phase behavior over a range of frequencies approaching three decades.

Algorithms↗
PubMed2001

Expression of the human glucocorticoid receptor alpha and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone.

Two isoforms of the human glucocorticoid receptor (hGR) have been described, hGRalpha and hGRbeta. We analyzed the expression and regulation of both hGR isoforms in human respiratory epithelial cells (BEAS-2B, A549, and primary nasal epithelial cells). In BEAS-2B cells, the expression of hGRalpha messenger RNA (mRNA) was much higher than that of hGRbeta mRNA. Dexamethasone (DEX) (10(-6) M) downregulated hGRalpha mRNA at 6 and 24 h (55 +/- 8 and 58 +/- 5% of control, respectively; P < 0.01), whereas it decreased hGRbeta mRNA only at 6 h (55 +/- 7% of control; P < 0.01). Downregulation of hGRalpha and hGRbeta mRNAs occurred even in the presence of cycloheximide. Actinomycin-D studies revealed that DEX enhanced the stabilization of hGRalpha and hGRbeta messages. hGRalpha but not hGRbeta protein was detected in BEAS-2B, A549, and nasal epithelial cells. After 24 h of incubation, 10(-6) M DEX decreased the expression of hGRalpha protein in BEAS-2B, A549, and nasal epithelial cells (16 +/- 4, 14 +/- 4, and 28 +/- 7% of control, respectively; P < 0.01). These results suggest that in respiratory epithelial cells: (1) hGRalpha is much more expressed than hGRbeta at both the mRNA and protein levels; (2) hGRalpha is downregulated by corticosteroids both in cell lines (BEAS-2B, A549) and in nasal primary cells; and (3) transcriptional, post-transcriptional, and post-translational mechanisms appear to be involved in the regulation of hGR expression by corticosteroids.

Animals↗
PubMed2000

Regulation of cyclooxygenase-1 and -2 expression in human nasal mucosa. Effects of cytokines and dexamethasone.

BACKGROUND: Cyclooxygenase (COX) converts arachidonic acid in prostanoids. COX exists in two isoforms, COX-1 is the constitutive whereas COX-2 is the inducible isoform. The regulation of COX-1 and COX-2 expression in nasal mucosa has not been previously reported. AIM: We studied expression and regulation by cytokines and corticosteroids of COX-1 and COX-2 in human nasal mucosa. Cultured human nasal explants from patients undergoing corrective nasal mucosal resection were examined for COX-1 and COX-2 expression by semiquantitative competitive PCR and Western blot. METHODS: Explants were incubated with pro-(IFNgamma, IL-1beta, and TNF-alpha) and anti(IL-10) inflammatory cytokines and dexamethasone. The mechanisms which regulate COX-2 mRNA expression were studied using inhibitors of translation (Actinomycin D) and transcription (Cicloheximide). RESULTS: The baseline expression of COX-2 mRNA was higher than COX-1 mRNA. Once in culture, there was a slight spontaneous up-regulation of COX-1 and a strong COX-2 mRNA and protein up-regulation. The incubation of nasal explants with pro-inflammatory cytokines increased the expression of COX-2 mRNA and protein, from 1 to 24 h of incubation in a dose-related manner. The regulation of these effects occurred at both transcriptional and post-transcriptional levels. Dexamethasone and IL-10 abrogated cytokine-induced COX-2 mRNA and protein expression. Pro-inflammatory cytokines, dexamethasone and IL-10 had no effect on COX-1 mRNA expression. CONCLUSIONS: As prostanoids have important regulatory effects on the immunologically mediated inflammatory responses, our findings throw some light on the mechanisms that regulate the enzymes which produce these metabolites in the human airway.

Adult↗
PubMed2000

Inhibition of GM-CSF secretion by topical corticosteroids and nedocromil sodium. A comparison study using nasal polyp epithelial cells.

Nasal epithelial cells maintain eosinophil survival by secreting granulocyte/macrophage colony-stimulating factor (GM-CSF). Corticosteroids antagonize eosinophil viability induced by GM-CSF. We investigated the effect of topical corticosteroids and nedocromil sodium on the release of GM-CSF from nasal polyp epithelial cells. Epithelial cells were obtained from 19 patients undergoing nasal polypectomy and cultured. After reaching confluence, cultured cells were stimulated with 10% foetal calf serum in the absence and presence of four topical corticosteroids and nedocromil sodium for 48 h. GM-CSF was measured by enzyme linked immunosorbent assay (ELISA). Fluticasone propionate was the most potent inhibitor of GM-CSF release (IC25 = 46 pM) closely followed by budesonide (IC25 = 4 nM), beclomethasone dipropionate (IC25 = 40 nM) and triamcinolone acetonide (IC25 = 75 nM). Nedocromil sodium had no effect on GM-CSF release. We conclude that the effect of topical steroids on reducing eosinophil infiltration in nasal polyps may be due in part to downregulation, among other cytokines, of epithelial GM-CSF production which prolongs eosinophil viability. Quantitatively, fluticasone propionate inhibited GM-CSF production more potently than budesonide, beclomethasone dipropionate and triamcinolone acetonide.

Administration, Topical↗
PubMed2000

Effects of topical glucocorticoids on in vitro lactoferrin glandular secretion: comparison between human upper and lower airways.

BACKGROUND: Mucus hypersecretion is a hallmark of upper and lower airway diseases, such as rhinitis, asthma, and chronic obstructive pulmonary disease. Although topical glucocorticoids are widely used to treat mucosal inflammation, their effect on mucus hypersecretion remains uncertain. OBJECTIVE: The aim of this study was to investigate the effect of budesonide and beclomethasone dipropionate on in vitro lactoferrin glandular secretion from both human nasal and bronchial mucosa and the potential mediating role of lipocortin 1. METHODS: Nasal and bronchial explants obtained from patients undergoing surgery were cultured in a controlled atmosphere. Lactoferrin (ELISA) was measured in culture supernatants, and lipocortin 1 (Western blot) was analyzed in explant tissues. RESULTS: Both budesonide and beclomethasone dipropionate (10(-6) mol/L) decreased spontaneous lactoferrin secretion in nasal and bronchial mucosa. The maximum effect of cortico-steroids (10(-6) mol/L) was obtained at day 3 in bronchial mucosa (budesonide: -56% +/- 9%, P <.05; beclomethasone dipropionate: -32% +/- 6%, P <.05) and at day 5 in nasal mucosa (budesonide: -34% +/- 10%, P <.05; beclomethasone dipropionate: -37% +/- 10%, P <.05). Methacholine (10(-4) mol/L) increased lactoferrin secretion in both bronchial (248% +/- 72%, P <.05) and nasal (107% +/- 28%, P <.05) explants, with this effect being completely abrogated by atropine. Budesonide caused a dose-related inhibitory effect on methacholine-induced lactoferrin secretion that was similar in both bronchial (down to -86% at 10(-6) mol/L) and nasal (down to -73% at 10(-6) mol/L) mucosa. Budesonide (10(-6) mol/L) did not show any effect on lipocortin 1 expression. CONCLUSIONS: These results suggest that glucocorticoid effects on airway inflammation may include a reduction of mucus hypersecretion in both nasal and bronchial mucosa.

Administration, Topical↗
PubMed2000

Intranasal challenge with aspirin in the diagnosis of aspirin intolerant asthma: evaluation of nasal response by acoustic rhinometry.

BACKGROUND: Nasal provocation tests with lysine-aspirin have recently been introduced for assessment of aspirin intolerant asthma. A study was undertaken to evaluate the usefulness of acoustic rhinometry, a new non-invasive technique, in the diagnosis of aspirin intolerant asthma/rhinitis. METHODS: Fifteen patients with aspirin intolerant asthma/rhinitis (nine women, mean (SD) age 54.7 (14) years), eight patients with aspirin tolerant asthma/rhinitis (three women, mean (SD) age 52.6 (7.8) years), and eight healthy subjects (two women, mean (SD) age 32.5 (9.7) years) were studied. All subjects were challenged with saline (0.9% NaCl) and 25 mg lysine acetylsalicylic acid (L-ASA) instilled into each nostril of the nose on two separate days. The clinical response was evaluated based on nasal symptoms (sneezes, itching, secretion and blockage). The nasal response was measured by acoustic rhinometry. Symptoms and rhinometry curves were recorded at 10 minute intervals for three hours, one hour before challenge and two hours after challenge. RESULTS: L-ASA challenge induced a significant increase in symptoms in patients with aspirin intolerant asthma/rhinitis. No differences in the clinical response were detected in those with aspirin tolerant asthma/rhinitis or healthy subjects. L-ASA challenge induced a significant decrease in nasal volume measured by acoustic rhinometry in aspirin intolerant patients. No differences were detected between the challenges in aspirin tolerant patients. If a 25% decrease in nasal volume is taken as the cut off point, the specificity of the test was 94% and the sensitivity reached 73%. The nasal challenge was well tolerated by all subjects. CONCLUSION: Acoustic rhinometry may be used to study the nasal response to L-ASA. Nasal challenge with L-ASA is safe and can be used as a diagnostic test even in asthmatic patients with severe bronchial obstruction.

Administration, Intranasal↗
PubMed1999

Lipid and protein metabolism in asthma. Effects of diet and corticosteroid therapy.

BACKGROUND: Because little is known about the effects of asthma and asthma therapy on lipid and protein metabolism, we have investigated the characteristics of diet and plasma/serum levels of fat and protein in a group of asthma patients with various degrees of severity. METHODS: A case-control study was carried out on 118 asthma patients recruited from an outpatient clinic and 121 healthy subjects. Asthma severity was characterized in four groups according to clinical symptoms, lung-function tests, and therapy. Normal dietary intake was estimated from a food frequency questionnaire. Serum protein, albumin, and fatty acids were determined by standard methods. RESULTS: The dietary energy intake of the asthmatics was significantly lower than that of the controls. However, no differences in the body mass index were found between asthma patients and healthy subjects. There were no differences in serum/plasma levels in any of the measured biochemical parameters between healthy subjects and asthmatics. Plasma levels of protein and albumin were significantly lower in severely corticosteroid-dependent patients. There was a significant negative correlation between plasma protein (r=0.36, P<0.05) and plasma albumin levels (r=0.43, P<0.01) and the daily dose of oral corticosteroids. We did not find any differences in plasma levels of cholesterol, HDL-cholesterol, LDL-cholesterol, and fatty acids between cortico-dependent patients and those not receiving this therapy. No correlation was found between any biochemical parameters and the daily dose of inhaled corticosteroids. CONCLUSIONS: Our results suggest that asthma induces a decrease in energy intake that does not result in a decreased body weight. Inhaled corticosteroids do not exert any metabolic effect, whereas severe asthma with regular oral corticosteroid therapy is associated with reduced plasma protein and albumin levels.

Administration, Oral↗
PubMed1999

Regulation of ICAM-3 and other adhesion molecule expressions on eosinophils in vitro. Effects of dexamethasone.

BACKGROUND: ICAM-3 has been recently identified as the third leukocyte-function associated-1 (LFA-1) ligand. ICAM-3 is expressed in eosinophils, but its regulation has not been studied. The objective of this study was to investigate the differential expression of ICAM-3 and other adhesion molecules (AM) on the surface of eosinophils. We also evaluated the effects of dexamethasone on AM expression. METHODS: Normodense eosinophils were isolated from peripheral blood and incubated with calcium ionophore A23187 (calcimycin) with and without dexamethasone. Expression of AM was assessed by flow cytometry and expressed as fluorescence mean intensity (FMI). RESULTS: Peripheral blood eosinophils constitutively expressed low levels of ICAM-1 and ICAM-2 (<10 FMI), moderate levels (10-50 FMI) of CD29 and L-selectin, and high levels (>50 FMI) of ICAM-3, LFA-1, and Mac-1. Calcium ionophore (1 microM) significantly increased Mac-1 and ICAM-1 expression at 6 and 24 h. L-selectin expression decreased at 6 and 24 h, but ICAM-2, ICAM-3, LFA-1, and CD29 expression did not show any significant change after calcium ionophore stimulation. Dexamethasone decreased ICAM-3 and increased L-selectin basal expression, and it caused a dose-related inhibition of calcium ionophore-induced ICAM-1 expression. CONCLUSIONS: These findings suggest that some AM, such as ICAM-1, Mac-1, and L-selectin, may be involved in adhesion during eosinophil activation and that glucocorticoids may prevent airway inflammation by regulating the expression of AM in eosinophils. The role of ICAM-3, a leukocyte AM highly expressed in resting eosinophils, remains to be clarified.

Antigens, CD↗
PubMed1999

Cyclooxygenase-2 mRNA is downexpressed in nasal polyps from aspirin-sensitive asthmatics.

Exogenous prostaglandin E2 (PGE2) given by inhalation almost completely abrogates aspirin-induced asthma and the accompanying increase in cysteinyl-leukotrienes production. Cyclooxygenase (COX) may be present in cells in both constitutive (COX-1) and inducible (COX-2) forms. To increase the production of the potentially protective endogenous PGE2, COX-2 should be upregulated. We hypothesize that an abnormal regulation of COX-2 will predispose patients with asthma to develop aspirin-intolerant asthma/rhinitis (AIAR). We therefore examined the expression of COX-2 messenger RNA (mRNA) in healthy nasal mucosa (n = 11) and in nasal polyps from both patients with AIAR (n = 8) and those with aspirin-tolerant asthma/rhinitis (ATAR) (n = 20). After total mRNA extraction, COX-1 and COX-2 mRNA expression were measured using a reverse transcriptase (RT)-semiquantitative PCR technique. Hybrid primers of COX-1. glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or COX-2. GAPDH were used to create PCR products that were cloned and used as internal standard controls in the competitive PCR reaction. Results are presented as mean +/- standard error of 10(6) molecules of mRNA/micrograms of total RNA. No differences in COX-1 mRNA expression were found between nasal mucosa and nasal polyps from both patients with ATAR and those with AIAR. However, COX-2 mRNA expression in nasal polyps from the AIAR group (0.38 +/- 0.10) was markedly and significantly lower than in polyps from the ATAR group (2.93 +/- 0. 52, sevenfold, p < 0.0001) and nasal mucosa (2.10 +/- 0.54, sixfold, p < 0.01). These findings suggest that an inadequate COX-2 regulation may be involved in AIAR.

Adult↗
PubMed1997

[Eosinophil activation by epithelial cells of the respiratory mucosa. Comparative study of normal mucosa and inflammatory mucosa].

BACKGROUND: To investigate the effect of epithelial cells from respiratory mucosa on eosinophil activation. PATIENTS AND METHODS: Epithelial cell cultures were obtained from healthy nasal mucosa and nasal polyps. Eosinophils were isolated from peripheral blood and incubated with epithelial cell conditioned media (HECM) in the presence or absence of dexamethasone (10 microM). Eosinophil survival, expression of EG2 and CD69, and production of eosinophil cationic protein (ECP) and leukotriene C4 (LTC4) were evaluated. Cytokine levels in HECM were assessed by ELISA. RESULTS: HECM induced eosinophil survival (78.6 +/- 9.9% for nasal mucosa, and 92.6 +/- 15% for nasal polyps) compared to controls (1 +/- 0.8%; p < 0.05). Dexamethasone blocked HECM induced eosinophil survival, this effect being greater when eosinophils were primed with nasal mucosa HECM. HECM promoted EG2 expression in eosinophils (47.9 +/- 9.1% for nasal mucosa, and 58.5 +/- 11.8% for nasal polyp) compared to controls (8.1 +/- 3.7%; p < 0.01). HECM had no effect on both CD69 expression and LTC4 release but decreased ECP secretion. Levels of interleukin (IL)-8 (35,700 +/- 7,300 pg/ml), IL-1 beta (11.3 +/- 1.8 pg/ml) and TNF-alpha (38.2 +/- 11 pg/ml) on nasal polyps HECM were significantly higher than on nasal mucosa HECM (17,600 +/- 2,700, 5.4 +/- 0.7 and 16.8 +/- 1.4 pg/ml, respectively; p < 0.05). CONCLUSIONS: Epithelial cells from respiratory mucosa proved to have potential to increase eosinophil survival and activation. The lower inhibitory effect of dexamethasone on nasal polyps induced eosinophil survival and activation may be caused by a higher release of eosinophil activating factors from nasal polyp epithelial cells (inflammed tissue) compared to nasal mucosa.

Antigens, CD↗
PubMed1997

Vasoactive intestinal peptide (VIP) induces IL-6 and IL-8, but not G-CSF and GM-CSF release from a human bronchial epithelial cell line.

Vasoactive intestinal polypeptide (VIP) is a 28-amino acid neuropeptide with vasodilator, bronchodilator, and anti-inflammatory effects. Little is known about pro-inflammatory effects of VIP. We investigated the effect of VIP on the secretion of IL-6, IL-8, GM-CSF, and G-CSF from a bronchial epithelial cell line (BEAS 2B). The incubation of BEAS-2B cells with VIP in concentrations of 10(-13) to 10(-7) M for 4 h, caused dose-related increases of IL-6 (98% increase above control, P < 0.001) and IL-8 (35% increase above control, P < 0.01). After 4 h of incubation, 10(-7) M PHI also increased IL-6 release by 74% (P < 0.01). After 8 h of incubation, VIP increased IL-6 release by 59% (P < 0.01), causing no effect on IL-8 release. After 24 h of incubation, VIP increased the release of IL-6 by 48% (P < 0.05) and IL-8 by 45% (P < 0.05). Ribonuclease protection assays for steady-state IL-6 mRNA revealed that increases in response to VIP stimulation occurred by 1 h and persisted through 16 h of stimulation. VIP had no significant effect on the release of G-CSF and GM-CSF. VIP did not induce cell proliferation at 24 and 48 h. These findings suggest that VIP can alter epithelial cell cytokine release and might be capable of modulating the airway inflammatory response in this manner.

Bronchi↗
PubMed1997

Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil survival and GM-CSF secretion.

Topical anti-inflammatory drugs decrease eosinophil infiltration. This action may be due to an effect on the release of epithelial cell products responsible for promoting eosinophil survival. We investigated the effect of fluticasone propionate, budesonide, beclomethasone dipropionate and nedocromil sodium on the release of granulocyte/macrophage colony-stimulating factor (GM-CSF) and on eosinophil survival induced by secretions from cultured nasal epithelial cells. Human epithelial cell-conditioned media (HECM) were generated by cultured epithelial cells obtained from healthy subjects undergoing corrective nasal surgery. Normodense eosinophils isolated from peripheral blood were incubated with HECM generated with and without the drugs. All of the drugs tested inhibited eosinophil survival, and response was dose-dependent. Fluticasone propionate had the highest inhibitory potency (25% inhibitory concentration (IC25) 1x10(-9) M), followed by budesonide (IC25 3.3x10(-8) M), beclomethasone dipropionate (IC25 1.5x10(-6) M), and nedocromil sodium IC25 5x10(-6) M). Likewise, fluticasone was the strongest steroid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M), followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25 13x10(-8) M), and nedocromil sodium (IC25 >10(-5) M). A significant correlation was found between both inhibitory effects (r=0.955; p<0.05). Topical anti-inflammatory drugs may decrease eosinophil survival by abrogating the promoting effect of epithelial cells. These drugs may exert part of their therapeutic effect by modulating GM-CSF release. The following rank of potency was observed: fluticasone propionate > budesonide > beclomethasone dipropionate > nedocromil sodium. The study of the interaction between epithelial cells and eosinophils may be a useful method for investigating and comparing the potency of topical drugs.

Administration, Topical↗
PubMed1997

Effects of topical anti-inflammatory drugs on eosinophil survival primed by epithelial cells. Additive effect of glucocorticoids and nedocromil sodium.

BACKGROUND: Eosinophil infiltration is a hallmark of the inflammatory response in rhinitis and in nasal polyposis. OBJECTIVE: We studied the effect of steroids and nedocromil sodium on eosinophil survival primed by epithelial cells from healthy (nasal mucosa) and inflamed (nasal polyp) respiratory tissue. METHODS: Blood eosinophils were incubated with increasing concentrations (10(-11)-10(-5) M) of topical steroids (fluticasone propionate, budesonide, triamcinolone acetonide and beclomethasone dipropionate) and/or nedocromil sodium prior to the addition of human epithelial cell conditioned media (HECM), eosinophil viability was measured and IC50 for each drug was calculated. RESULTS: All four steroids and nedocromil sodium caused a dose-related inhibition of HECM-induced eosinophil survival. The IC50 of steroids were lower in eosinophils primed by mucosa HECM than on those primed by polyp HECM (fluticasone, 4 nM vs 114 nM; budesonide, 21 nM vs 280 nM; triamcinolone, 7 nM vs 853 nM; and beclomethasone, 171 nM vs 181 nM). The combined inhibitory effect of 10(-7) M budesonide plus 10(-5) M nedocromil (43.8 +/- 10.8%, P<0.03) was significantly higher than budesonide (28.5 +/- 9.2%) or nedocromil (16.7 +/- 5.4%) alone and close to 10(-5) M budesonide (52.3 +/- 11%). No differences were found in cytokine (IL-8, IL-6, GM-CSF, TNF alpha, IL-1beta and RANTES) concentrations between HECM from mucosa and polyps. CONCLUSION: These results suggest that topical anti-inflammatory drugs may diminish airway eosinophilic infiltration by decreasing eosinophil viability, that nasal polyp epithelial cell secretions may induce steroid resistance in eosinophils, and that nedocromil sodium has additive effects with steroids.

Administration, Topical↗
PubMed1996

Endothelin-1 induces GM-CSF, IL-6 and IL-8 but not G-CSF release from a human bronchial epithelial cell line (BEAS-2B).

Endothelin (ET) is a powerful vasoconstrictor and bronchoconstrictor peptide that may be involved in the pathogenesis of bronchial asthma. We have investigated the effect of ET on the secretion of IL-6, IL-8, GM-CSF and G-CSF in a bronchial epithelial cell line (BEAS-2B). Incubation of BEAS-2B cells with ET-1 (10(-13) to 10(-7) M) for 4 h caused dose-related increases in the release of IL-8 (68% increase above control, P < 0.001) and IL-6 (43% increase above control, P < 0.001), compared to untreated control cells. After 48 h incubation, ET-1 also increased the release of IL-8 by 35% (P < 0.001) and GM-CSF by 38% (P < 0.01). ET-1 had no significant effect on G-CSF release. ET-1 did not induce cell proliferation at 24 or 48 h. Since ET-immunoreactive materials are expressed in epithelial cells in asthma, it is possible that ET-1 of epithelial origin may act in a paracrine or autocrine fashion on airway epithelial ET receptors to stimulate IL-8, IL-N6 and GM-CSF release. Thus, ET-1 may play a role in the regulation of the cytokine responses involved in inflammation of the airway mucosa.

Bronchi↗