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Biomedical subjects

Geert M Verleden

Publications and source records attributed to Geert M Verleden.

At least 19 recordsLinked to original sources
PubMed2006

Comparative study of donor lung injury in heart-beating versus non-heart-beating donors.

OBJECTIVE: The use of non-heart-beating donors (NHBD) has been advocated as an alternative to overcome the critical organ shortage in lung transplantation despite the warm ischemic period that may result in primary graft dysfunction. On the contrary, brain death in the heart-beating donor (HBD) may be an underestimated risk factor for donor lung injury. We postulated that 60 min of warm ischemia in the NHBD is less detrimental to the lung than the pathophysiological changes after brain death in the HBD. In this study we compared the quality of lungs from HBD versus NHBD in an isolated reperfusion model. METHODS: Pigs (n=10 per group) were divided into three groups. In group I (HBD), brain death was induced by acute inflation of an intracranial epidural balloon catheter. In group II (CONTROL), the balloon was not inflated. In group III (NHBD), cardiac arrest was induced by myocardial fibrillation. After 5 h of in situ mechanical ventilation, lungs in HBD and CONTROL were preserved with a cold antegrade flush. In NHBD, unflushed grafts were explanted after 1 h of warm ischemia and 4 h of topical cooling in the cadaver. Graft performance was evaluated during 1 h in an isolated ventilation and reperfusion model. Extravascular lung water content (EVLW) was calculated. All data are reported as mean+/-SEM. RESULTS: A significant autonomic storm was observed in HBD following balloon inflation. During ex vivo assessment, pulmonary vascular resistance (PVR) at 60 min in HBD (2634+/-371 dynes cm(-5)) was significantly higher as compared with that of CONTROL and NHBD (1894+/-137 dynes s cm(-5) and 1268+/-111 dynes s cm(-5), respectively; p<0.05). Plateau airway pressure (Plateau AwP) was also higher in HBD (17+/-1cmH2O) compared with that of CONTROL (12+/-1 cmH2O; p<0.05) and NHBD (14+/-1 cmH2O; not significant). No significant differences were observed between HBD, CONTROL and NHBD in EVLW (79+/-1%, 79+/-0% and 78+/-1%, respectively), and in PO2/FiO2 (564+/-58 mmHg, 622+/-14 mmHg and 578+/-26 mmHg, respectively). CONCLUSIONS: These data indicate that 1-h warm ischemic lungs in our model are less susceptible to ischemia-reperfusion injury than lungs retrieved 5 h after brain death. This study further supports the use of lungs from NHBD for pulmonary transplantation.

Airway Resistance↗
PubMed2006

Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome.

RATIONALE: Bronchiolitis obliterans syndrome (BOS) remains the leading cause of death after lung transplantation. Treatment is difficult, although azithromycin has recently been shown to improve FEV(1). The exact mechanism of action is unclear. HYPOTHESES: (1) Azithromycin reduces airway neutrophilia and interleukin (IL)-8 and (2) airway neutrophilia predicts the improvement in FEV(1). METHODS: Fourteen lung transplant patients with BOS (between BOS 0-p and BOS 3) were treated with azithromycin, in addition to their current immunosuppressive treatment. Before and 3 mo after azithromycin was introduced, bronchoscopy with bronchoalveolar lavage (BAL) was performed for cell differentiation and to measure IL-8 and IL-17 mRNA ratios. RESULTS: The FEV(1) increased from 2.36 (+/- 0.82 L) to 2.67 L (+/- 0.85 L; p = 0.007), whereas the percentage of BAL neutrophilia decreased from 35.1 (+/- 35.7%) to 5.7% (+/- 6.5%; p = 0.0024). There were six responders to azithromycin (with an FEV(1) increase of > 10%) and eight nonresponders. Using categorical univariate linear regression analysis, the main significant differences in characteristics between responders and nonresponders were the initial BAL neutrophilia (p < 0.0001), IL-8 mRNA ratio (p = 0.0009), and the postoperative day at which azithromycin was started (p = 0.036). There was a significant correlation between the initial percentage of BAL neutrophilia and the changes in FEV(1) after 3 mo (r = 0.79, p = 0.0019). CONCLUSION: Azithromycin significantly reduces airway neutrophilia and IL-8 mRNA in patients with BOS. Responders have a significantly higher BAL neutrophilia and IL-8 compared with nonresponders and had commenced treatment earlier after transplantation. BAL neutrophilia can be used as a predictor for the FEV(1) response to azithromycin.

Adult↗
PubMed2006

Impact of warm ischemia on different leukocytes in bronchoalveolar lavage from mouse lung: possible new targets to condition the pulmonary graft from the non-heart-beating donor.

BACKGROUND: The use of non-heart-beating donors (NHBDs) for lung transplantation is a possible alternative for increasing the number of organs available. The warm ischemic period after circulatory arrest may contribute to a higher degree of primary graft dysfunction, resulting from ischemia-reperfusion injury (IRI). A better understanding of the role of inflammatory cells during the warm ischemic interval may be useful for developing new therapeutic strategies against IRI. METHODS: Mice were divided in 7 groups (n = 6/group). In 3 groups, ischemia was induced by clamping the hilum of the left lung for 30, 60 or 90 minutes (Groups [30I], [60I] or [90I], respectively). In 3 more groups, the lung was reperfused for 4 hours after identical ischemic intervals (Groups [30I+R], [60I+R] or [90I+R], respectively). Surgical impact was evaluated in a sham group ([sham]). Total and differential cell counts and interleukin-1beta (IL-1beta) protein levels in bronchoalveolar lavage (BAL) were determined and their correlations were investigated. RESULTS: Total cell, macrophage and lymphocyte numbers and IL-1beta protein levels increased progressively with longer ischemic intervals. A significant rise in BAL macrophages and lymphocytes was observed between [60I] and [90I] (p < 0.01 and p < 0.001, respectively). BAL neutrophils only increased after reperfusion with longer ischemic intervals. A positive correlation was found in the ischemic groups between IL-1beta levels and the number of macrophages (r = 0.62; p = 0.0012) and the number of lymphocytes (r = 0.68; p = 0.0002). A positive correlation was found in the reperfusion groups between IL-1beta levels and the number of neutrophils (r = 0.48; p = 0.044). CONCLUSIONS: This study demonstrates for the first time that BAL macrophages and lymphocytes increase significantly during warm ischemia and correlate with IL-1beta levels.

Animals↗
PubMed2005

Fatal Scopulariopsis infection in a lung transplant recipient: a case report.

A case of a fatal Scopulariopsis infection is reported in a 63-year-old lung transplantation patient with a 7-week history of dyspnea that presented initially with pericardial and pleural fluid. Because of a respiratory arrest, the patient was intubated and received positive pressure ventilation. Later, obstructive shock developed due to a pericardial tamponade requiring pericardectomy and then urgent extracorporal membrane oxygenation. The working hypothesis was of disseminated cytomegalovirus infection because cultures from bronchoalveolar lavage and transbronchial biopsy specimens were positive. The pericardial biopsy specimen showed fungal hyphae. After the patient died from the infection, the fungus was identified as Scopulariopsis acremonium. This case report describes the first case, to our knowledge, of an insidious Scopulariopsis acremonium infection in an immunocompromised lung transplant patient, underscoring the importance of a direct, invasive approach and early treatment with anti-fungal therapy in immunocompromised patients.

Ascomycota↗
PubMed2005

Effects of long-acting bronchodilators and placebo on histamine-induced asthma symptoms and mild bronchusobstruction.

STUDY OBJECTIVE: Accurate perception of airway caliber remains an important issue in asthma management. The way bronchodilation is perceived is partly related to the perception of the efficacy of bronchodilators in relieving complaints. In the present study, we compared the effects of salmeterol, formoterol and placebo on relief of histamine-induced asthma symptoms and mild bronchusobstruction. METHODS: In this randomized controlled, double blind study, 30 asthmatics were challenged with histamine until forced expiratory volume in 1s (FEV(1)) fell with > or =20%. Subjects received salmeterol, formoterol or placebo after the histamine provocation. Pulmonary function (FEV(1)) and asthma symptoms (Asthma Symptom Checklist, Borg Dyspnea Scale) were assessed 5 and 20 min later. RESULTS: FEV(1) improved significantly more in the salmeterol and formoterol group than in the placebo group (P<0.001, P<0.001 and P<0.05, respectively). Salmeterol and formoterol were not different with regard to the pulmonary function recovery. No significant differences were found between the effects of salmeterol, formoterol and placebo on any of the symptom responses at the different time points. CONCLUSIONS: We conclude that after a histamine-induced mild bronchusobstruction, a similar asthma symptom recovery occurred when inhaling salmeterol, formoterol or placebo, despite better recovery of pulmonary function in the active drug conditions.

Adult↗
PubMed2005

IL-1beta in bronchial lavage fluid is a non-invasive marker that predicts the viability of the pulmonary graft from the non-heart-beating donor.

BACKGROUND: Viability testing of the pulmonary graft retrieved from the non-heart-beating donor (NHBD) is mandatory for successful outcome after lung transplantation. Functional assessment by ex vivo reperfusion, however, remains a cumbersome procedure. In this study, therefore, we wanted to investigate the possible value of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) measured in bronchial lavage fluid (BLF) in predicting functional outcome of the pulmonary graft after reperfusion. METHODS: Domestic pigs (29.9 +/- 0.56 kg) were sacrificed and divided in 5 groups (n = 5/group). In the non-ischemic group (NHBD-0), the heart-lung block was explanted immediately. In the other groups the animals were left untouched with increasing time intervals (1 hour = NHBD-1; 2 hours = NHBD-2; 3 hours = NHBD-3). Thereafter both lungs were cooled topically via chest drains up to a total ischemic interval of 4 hours. Finally, in the heart-beating donor group lungs were flushed and stored for 4 hours (4 degrees C) [HBD]. BLF samples were taken from the right lung in all groups after explantation for measurement of IL-1beta and TNF-alpha and the left lung was prepared for evaluation in an isolated reperfusion circuit. Haemodynamic, aerodynamic and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Graft function deteriorated with increasing time intervals after death. A strong correlation was found between the increase of IL-1beta concentration measured in BLF and the increase in pulmonary vascular resistance (r = 0.80), mean airway pressure (r = 0.74) and wet-to dry weight ratio (r = 0.78); (p < 0.0001, for all parameters). No significant differences in TNF-alpha levels in BLF were observed amongst groups (p = 0.933). CONCLUSIONS: IL-1beta in BLF prior to reperfusion correlated well with graft function and may therefore be a useful, non-invasive marker that can predict the viability of the pulmonary graft from the NHBD.

Animals↗
PubMed2005

Interleukin-17--induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB.

BACKGROUND: It has recently become clear that interleukin (IL)-8 plays a role in chronic neutrophilic inflammatory disorders, such as chronic rejection after lung transplantation. We have shown that IL-17--stimulated human airway smooth muscle cells (HASMC) are able to produce IL-8. The aim of this study was to determine whether p38 mitogen-activated protein kinase (MAPK), c-Jun amino-terminal kinase (JNK), p42/p44 extracellular signal-related kinase (ERK) and nuclear factor-kappaB (NF-kappaB) are involved in IL-17--induced IL-8 production in HASMC in vitro. METHODS: We used human airway smooth muscle cells in culture. Western blotting was done to obtain data regarding activation of MAPK. Furthermore, we used specific inhibitors of MAPK to investigate their involvement in IL-17--induced IL-8 release, which was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Western blotting clearly demonstrated that p38 MAPK, JNK and p42/p44 ERK were activated by IL-17 in HASMC. Using SB203580, a specific inhibitor of p38 MAPK, we detected a concentration-dependent inhibition of IL-17--induced IL-8 production with a maximal decrease of 63 +/- 5% (n=8, p<0.01). Curcumin, a specific inhibitor of JNK, also concentration-dependently reduced IL-17--induced IL-8 production, with a maximal decrease of 82+/-4% (n=8, p<0.01). U0126, a specific inhibitor of p42/p44 ERK, induced a maximal decrease of 84+/-5% (n=8, p<0.001). Pyrrolydine dithiocarbamate (PDTC), an inhibitor of NF-kappaB, caused a 70+/-5% (n=8, p<0.01) decrease in IL-17--induced IL-8 production. CONCLUSIONS: We found that IL-17 induces activation of p38MAPK, JNK and p42/p44ERK in HASMC. We also found that p38MAPK, JNK, p42/p44 ERK and NF-kappaB play an important role in IL-17--induced IL-8 production in HASMC in vitro. This may open up new opportunities for further treatment of this disease.

Blotting, Western↗
PubMed2005

Effect of azithromycin on bronchiectasis and pulmonary function in a heart-lung transplant patient with severe chronic allograft dysfunction: a case report.

Azithromycin has been shown to be beneficial in several diseases with chronic neutrophilic inflammation of the airways, such as cystic fibrosis and bronchiolitis obliterans syndrome (BOS) after lung transplantation. Up to now, however, its healing effect on bronchiectasis has never been demonstrated. We report a heart-lung transplant patient who developed chronic rejection (BOS stage 3) with the appearance of gross bronchiectasis on a spiral computed tomography (CT) chest scan. Within 2 weeks after starting azithromycin, the patient's forced expiratory volume in 1 second increased significantly and a repeat spiral CT chest scan 5 months later, showed a major improvement of the bronchiectasis. This case report illustrates that bronchiectasis may greatly improve after treatment with azithromycin and no longer needs to be considered an endstage finding in patients with severe BOS.

Adolescent↗
PubMed2005

Nebulized N-acetyl cysteine protects the pulmonary graft inside the non-heart-beating donor.

BACKGROUND: The use of lungs from non-heart-beating donors (NHBD) might significantly alleviate the organ shortage. The tolerable warm ischemic period after cardiac arrest, however, is limited to approximately 1 hour. If the lung could be safely protected inside the cadaver, this time period may be prolonged. This would help to obtain family consent and to organize organ retrieval. METHODS: Pigs (30.8 +/- 0.6 kg) were killed, left untouched for 3 hours, and divided into 3 groups. Nebulized N-acetyl cysteine (NAC) (300 mg), a precursor of the antioxidant agent glutathione, was administered during 10 minutes before death in Group I (NAC-NHBD, n = 6) and 15 minutes after death in Group II (NHBD-NAC, n = 6). In the control group, no aerosol was administered (NHBD, n = 6). After a warm ischemic interval of 3 hours, both lungs in all groups were topically cooled for 1 hour. Thereafter, the left lung was prepared for evaluation in an isolated reperfusion circuit. Hemodynamic, aerodynamic, and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. The right lung was used to measure reduced glutathione (GSH) and oxidized glutathione (GSSG) levels (micromol/g) in lung homogenates and total protein levels in bronchial lavage fluid. RESULTS: Pulmonary vascular resistance, mean airway pressure, and W/D were significantly decreased in NAC-NHBD (1930 +/- 144 Dynes x sec x cm(-5), 14.2 +/- 0.5 cm H2O, and 7.4 +/- 0.4; p < 0.01, 0.01, and 0.05, respectively) and NHBD-NAC (1837 +/- 180 Dynes x sec x cm(-5), 13.3 +/- 1.2 cm H2O, and 7.3 +/- 0.3; p < 0.01, 0.05, and 0.05, respectively) when compared with the control group (5051 +/- 530 Dynes x sec x cm(-5), 17 +/- 0.4 cm H2O, 8.5 +/- 0.1, respectively). GSH/GSSG ratio was significantly higher and protein levels were significantly lower in NAC-NHBD (1.7 +/- 0.1 and 1315 +/- 60 microg/ml; p < 0.05 and 0.05, respectively) and NHBD-NAC (1.7 +/- 0.2 and 1475 +/- 159 microg/ml; p < 0.05 and 0.05, respectively) when compared with the control group (1.2 +/- 0.1 and 2150 +/- 200 microg/ml). CONCLUSIONS: Nebulized NAC administered before or shortly after death attenuates early ischemia reperfusion injury via upregulation of glutathione. NAC might be a promising tool to protect the pulmonary graft from both controlled and uncontrolled NHBD.

Acetylcysteine↗
PubMed2004

Accuracy of exhaled nitric oxide measurements for the diagnosis of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Exhaled nitric oxide (eNO) is increased in patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation. However, the accuracy of eNO measurements in diagnosing BOS is unknown. METHODS: Thirty-two lung-transplant patients were included. Their immunosuppressive regimen consisted of cyclosporin A (tacrolimus), azathioprine (mycophenolate mofetil), and oral but no inhaled steroids. eNO levels and spirometry were prospectively followed until 2 years after transplantation or until the patient developed BOS. RESULTS: Thirteen patients (group A) developed BOS (607 +/- 158 days after transplantation). Their mean eNO level at that time was 24.3 +/- 13.2 parts per billion (ppb), whereas the eNO value in the stable patients at 2 years (group B) was 11.4 +/- 4.9 ppb, P=0.0054. All group A patients had an eNO of 15 or greater ppb. Seven patients of group B also had an eNO of 15 or greater ppb, resulting in a test accuracy for the diagnosis of BOS of 0.78. However, considering only those patients who had two consecutive measurements (3-6 weeks apart) of eNO 15 or greater ppb during the months preceding the diagnosis of BOS or in the whole 2-year evaluation period, only 3 of 19 patients in group B (false-positives) but 12 of 13 in group A (1 false-negative) now fulfilled that criteria, which became positive at a mean of 263 +/- 169 days before the diagnosis of BOS was met, based on the forced expiratory volume in 1 second criteria. This increased the accuracy to 0.88. CONCLUSION: Measurements of eNO appear to be an accurate test for the early diagnosis of BOS.

Adult↗
PubMed2004

Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the leading cause of late mortality after lung transplantation. METHODS: We added azithromycin (AZI) (250 mg/day for 5 days, followed by 250 mg every other day) to the current immunosuppressive therapy in eight lung transplant recipients (mean age 36 years) with established BOS in an attempt to prevent further decline of the forced expiratory volume in 1 sec (FEV1). RESULTS: Before the administration of AZI, there was a gradual decline of the FEV1 (-34.4%+/-14.7%) compared with the patients' best postoperative values. Twelve weeks after AZI had been added, there was a significant increase in the FEV1 (+18.3%+/-14.6%, P <0.0001, analysis of variance) with an absolute increase of 328+/-305 mL. This increase persisted in three patients during 9 months of follow-up. CONCLUSIONS: AZI is a promising drug for some patients with BOS after lung transplantation. The exact mechanism of action is unknown at the present time.

Adolescent↗
PubMed2004

How long can we preserve the pulmonary graft inside the nonheart-beating donor?

BACKGROUND: The use of lungs from nonheart-beating donors (NHBD) might significantly alleviate the organ shortage. Extending the preharvest interval in NHBD would facilitate distant organ retrieval. We hypothesized that prolonged topical cooling inside NHBD after 60 minutes of initial warm ischemia would not affect the pulmonary graft. METHODS: Domestic pigs were anesthetized and divided into three groups (n = 6 in each group). In the control group (HBD), lungs were flushed, explanted, and further stored in low potassium dextran solution (4 degrees C) for 4 hours. In the two study groups pigs were sacrificed by myocardial fibrillation and left untouched for 1 hour. Chest drains were then inserted for topical lung cooling (6 degrees C) for 3 hours (NHBD-TC3) or 6 hours (NHBD-TC6). The left lung in all groups was then prepared for evaluation. In an isolated circuit lungs were ventilated and reperfused through the pulmonary artery. Hemodynamic, aerodynamic, and oxygenation variables were measured 35 minutes after onset of controlled reperfusion. Wet-to-dry weight ratio was calculated. RESULTS: No significant differences were observed among the three groups in pulmonary vascular resistance (p = 0.38), mean airway pressure (p = 0.39), oxygenation index (p = 0.62), and wet-to-dry weight ratio (p = 0.09). CONCLUSIONS: These data confirm that 1 hour of warm ischemia does not affect the pulmonary graft from NHBD compared with HBD. The preharvest interval can be safely extended up to 7 hours postmortem by additional topical cooling of the graft inside the cadaver. This technique may facilitate distant organ retrieval in NHBD.

Animals↗
PubMed2004

N-acetylcysteine inhibits interleukin-17-induced interleukin-8 production from human airway smooth muscle cells: a possible role for anti-oxidative treatment in chronic lung rejection?

BACKGROUND: Long-term survival of lung transplantation is threatened by obliterative bronchiolitis, or its clinical equivalent, bronchiolitis obliterans syndrome. With a prevalence of >50% at 5 years after transplantation, it has emerged as the most significant long-term complication. Neutrophilic inflammation and increased interleukin (IL)-8 production seem to be part of the basic pathophysiologic mechanism of chronic rejection. Recently, it has been suggested that reactive oxygen species may also play an important role in the pathogenesis because they are known to induce smooth muscle proliferation. METHODS: Human airway smooth muscle cells in vitro were stimulated with IL-17 (0.1 to 10 ng/ml) or with IL-17 (10 ng/ml) and the anti-oxidative agent N-acetylcysteine (1 micromol/liter to 10 mmol/liter). Production of 8-isoprostane was measured with a commercially available enzyme immunoassay kit and production of IL-8 was measured using a standard enzyme-linked immunoassay technique. RESULTS: IL-17 produced a concentration-dependent increase in 8-isoprostane with a maximum of 136.5 +/- 15.5 pg/ml with IL-17 (10 ng/ml, p < 0.001, n = 12, vs unstimulated cells). N-acetylcysteine (NAC) was able to decrease IL-17-induced 8-isoprostane production, with a maximum decrease of 59.3 +/- 9% (p < 0.001, n = 12) with 10 mmol/liter of N-acetylcysteine, which also decreased IL-17-induced IL-8 production in a concentration-dependent manner (with maximum inhibition of 86.3% when combined with NAC 10 mmol/liter as compared with IL-17 alone). CONCLUSIONS: We demonstrated that human airway smooth muscle cells, when stimulated with IL-17, are able to produce 8-isoprostane, which could be inhibited by adding N-acetylcysteline, and which was also able to decrease IL-17-induced IL-8 production. The clinical significance of these in vitro findings for prevention or treatment of chronic rejection after lung transplantation remains to be investigated.

Acetylcysteine↗
PubMed2004

Non-heart-beating donors.

The widespread application of lung transplantation is limited by the shortage of suitable donor organs resulting in longer waiting times for listed patients with a substantial risk of dying before transplantation. To overcome this critical organ shortage, some transplant programs have now begun to explore the use of lungs from circulation-arrested donors, so called non-heart-beating donors (NHBDs). This review outlines the different categories of NHBDs, the relevant published experimental data that support the use of lungs coming from these donors and the clinical experience worldwide so far. Techniques for NHBD lung preservation and pretransplant functional assessment are reviewed. Ethical issues involved in transplanting lungs from asystolic donors are discussed.

Humans↗
PubMed2003

Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-kappaB in IL-1beta-induced chemokine release in human airway smooth muscle cells.

Asthma is an inflammatory disease, in which eotaxin, MCP-1 and MCP-3 play a crucial role. These chemokines have been shown to be expressed and produced by IL-1beta-stimulated human airway smooth muscle cells (HASMC) in culture. In the present study we were interested to unravel the IL-1beta-induced signal transduction leading to chemokine production. Using Western blot, we observed an activation of p38 MAPK, JNK kinase and p42/p44 ERK when HASMC were stimulated with IL-1beta. We also observed a significant decrease in the expression and the release of eotaxin, MCP-1 and MCP-3 in the presence of SB203580, an inhibitor of p38 MAPK (71 +/- 6%, P < 0.05, n = 8 and 39 +/- 10% P < 0.01, n = 10 respectively), curcumin, an inhibitor of JNK kinase (83 +/- 4.9% and 88 +/- 3.4% respectively, P < 0.01, n = 4). U0126, an inhibitor of p42/p44 ERK, also produced a significant decrease in chemokine production (46.3 +/- 9%, P < 0.01 n = 10 and 67.8 +/- 12%, P < 0.01, n = 12). Pyrrolydine dithiocarbamate, an inhibitor of NF-kappaB was also able to reduce the eotaxin, MCP-1 and MCP-3 expression and production (50 +/- 13%, P < 0.05, n = 10 and 23 +/- 7%, P < 0.05, n = 12). We conclude that p38 MAPK, JNK kinase, ERK and NF-kappaB are involved in the IL-1beta-induced eotaxin, MCP-1, and MCP-3 expression and release in HASMC.

Asthma↗