Biomedical subjects

Otylia Kowal-Bielecka

Publications and source records attributed to Otylia Kowal-Bielecka.

13 recordsLinked to original sources

PubMed2007

Mechanisms of Disease: leukotrienes and lipoxins in scleroderma lung disease--insights and potential therapeutic implications.

Scleroderma interstitial lung disease (SLD) is a leading cause of morbidity and mortality in patients with systemic sclerosis. Although the pathogenesis of SLD is not clear, excessive fibrosis and inflammatory cell infiltration are the main histologic features of this disorder. Leukotrienes and lipoxins are two functionally different classes of lipoxygenase-derived eicosanoids. Leukotrienes are potent proinflammatory mediators and directly and indirectly stimulate fibroblast chemotaxis, proliferation, and collagen synthesis. Lipoxins counter-regulate the proinflammatory actions of leukotrienes and activate resolution of the inflammatory response. In addition, lipoxins inhibit growth-factor-induced fibroblast proliferation and collagen synthesis. Studies using bronchoalveolar lavage have revealed that there is an overproduction of proinflammatory and profibrotic leukotrienes in the lungs of patients with SLD, and that leukotriene levels correlate with inflammatory indices within the lungs. Moreover, the increased levels of leukotrienes in these patients are not balanced by an upregulation of anti-inflammatory and antifibrotic lipoxins. Unopposed actions of leukotrienes might, therefore, induce chronic inflammation and fibrosis in the lungs of SLD patients. Accordingly, pharmacologic correction of a leukotriene-lipoxin imbalance using leukotriene inhibitors or lipoxin analogs might be a new approach to the treatment of SLD.

Cell Proliferation↗

PubMed2006

Monocyte chemoattractant protein 1 released from glycosaminoglycans mediates its profibrotic effects in systemic sclerosis via the release of interleukin-4 from T cells.

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1; CCL2) has been implicated in the pathogenesis of fibrotic diseases and is up-regulated in patients with systemic sclerosis (SSc). The aim of the present study was to examine the mechanisms by which MCP-1 mediates its profibrotic effects in the setting of SSc. METHODS: The expression of receptors for MCP-1 on dermal fibroblasts was analyzed by real-time polymerase chain reaction and fluorescence-activated cell sorting. The ability of extracellular matrix proteins to bind and release MCP-1 was quantified by enzyme-linked immunosorbent assay. Th0 cells were isolated using a magnetic-activated cell sorting system and were stimulated twice in the presence of MCP-1. The synthesis of collagen was measured using the Sircol collagen assay kit. RESULTS: The glycosaminoglycan chondroitin sulfate, but not fibronectin or collagens, bound and released MCP-1 in a time-dependent manner. MCP-1 that was released from chondroitin sulfate induced the differentiation of interleukin-4 (IL-4)-producing T cells in a dose-dependent manner. In turn, dermal fibroblasts from patients with SSc expressed IL-4 receptor, and stimulation with IL-4 significantly increased the production of collagen in dermal fibroblasts. In contrast, CCR2a and CCR2b, as well as D6 and US28 (other potential receptors of MCP-1), were not detectable in SSc and normal fibroblasts, and their expression was not induced by platelet-derived growth factor, IL-1beta, or IL-4. In addition, MCP-1 had no direct effects on collagen production by fibroblasts. CONCLUSION: MCP-1 has no direct effects on dermal fibroblasts but contributes to fibrosis in patients with SSc by inducing the differentiation of IL-4-producing T cells. Because MCP-1 has both proinflammatory and profibrotic effects, pharmacologic targeting of MCP-1 could be a promising therapeutic approach in SSc.

Adolescent↗

PubMed2006

Targeting vascular disease in systemic sclerosis.

Systemic sclerosis (scleroderma, SSc) is a chronic connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and a distinctive pattern of internal organ involvement. Excessive fibrosis, vascular injury, autoimmunity and inflammation are permanent features of the disease process leading to irreversible organ damage and significant morbidity and mortality in SSc patients. Recent progress in understanding the pathogenesis of SSc as well as diagnostic and therapeutic advances in medicine have made more effective treatment strategies possible. So far, therapies targeting vascular aspects of SSc have been most successful. This underlines the role of vascular injury in the pathogenesis of the disease and raising hopes of significant improvement in the management of SSc patients. The aim of this review is to summarize recent and potential future treatments of SSc-associated vascular disease.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

[Cyclophosphamide treatment in patients with systemic sclerosis].

Systemic sclerosis (SSc) is a chronic, multisystemic, connective tissue disease characterized by fibrosis of the skin and visceral organs and the impairment of blood vessels. The etiology of SSc is unknown and its pathogenesis unclear. Effective treatment of SSc is also unavailable. Cyclophosphamide (CFX) has been reported to exert some beneficial actions in SSc patients, in particular in those with interstitial lung disease. However, it should be kept in mind that CFX treatment is related to multiple side effects. The aim of this study was to review available literature concerning the use of CFX in SSc patients.

Cyclophosphamide↗

PubMed2006

[Secondary lethal catastrophic antiphospholipid syndrome in 24-years old female patient with overlap syndrome (systemic sclerosis and systemic lupus erythematosus)].

In our article we describe the case of 24 years old woman with overlap syndrome under form of systemic sclerosis and systemic lupus erythematosus complicated by secondary antiphospholipid syndrome (APS). The first manifestation of antiphospholipid syndrome was intrauterine fetal death. Afterwards pulmonary embolism occurred. After several weeks in result of catastrophic course of antiphospholipid syndrome coronary artery thrombosis and myocardial infarction occurred with following prominent left ventricle systolic failure and multi organ failure. The patient died about one month after discharge from the hospital.

Adult↗

PubMed2006

[Causes of death of patients with systemic sclerosis].

UNLABELLED: Systemic sclerosis (SSc) is a chronic, systemic connective tissue disease, characterized by progressive skin fibrosis, internal organs and disfunction blood vessels. THE AIM: of the study was o analyze death causes in patients with SSc and the assessment of relationship between clinical status, immunologic test results and survival/mortality of patients with SSc. MATERIAL AND METHODS: Case histories of all patients with SSc, hospitalized for six years (since 1'" October 1999 to 1It October 2005) in Department of Rheumatology and Internal Diseases, Medical University of Bialystok, were retrospectively analyzed. Current patients status at the end-point of study was estimated during control examination and phone contact in selected cases. The time and cause of death was based on autopsy results. RESULTS: In study group of 76 patients with SSc, 13 deaths were found (17,1%). Death cause analyses revealed that: interstitial lung disease was the main cause of death (4/13 - 30%). As a secondary cause of death in these patients neoplasms were recognized (3/13 - 23,1%). In all patients with neoplasms exudation in pleura was diagnosed. CONCLUSIONS: Pulmonary complications and neoplasms are predominant causes of death in patients with SSc. Risk factors of death are: pulmonary hypertension and myositis. The presence of exudation in pleura in patients with SSc is a bad prognostic symptom and a possible sign of neoplastic disease.

Adolescent↗

PubMed2005

Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis.

OBJECTIVE: To examine the expression and regulation of interleukin-21 (IL-21) and IL-21 receptor (IL-21R) in patients with systemic sclerosis (SSc; scleroderma). METHODS: Skin biopsy specimens were obtained from 23 patients with SSc and 15 healthy controls. IL-21/IL-21R messenger RNA (mRNA) was quantified using real-time polymerase chain reaction (PCR). The expression pattern of IL-21/IL-21R was analyzed by in situ hybridization and Western blotting. Stimulation experiments were performed with cultured dermal fibroblasts from patients with SSc and healthy controls as well as with keratinocytes, using IL-1beta, platelet-derived growth factor BB, monocyte chemoattractant protein 1, transforming growth factor beta, and IL-21. The SCID-hu skin mouse model was used for in vivo experiments. RESULTS: IL-21R mRNA was detected in all biopsy specimens from patients with SSc and controls, with a 4.7-fold increase observed in SSc samples. In situ hybridization and immunohistochemical analysis showed an up-regulation of IL-21R in samples of epidermis from SSc patients, whereas no signal was detected in skin specimens from healthy controls. These results were confirmed in vitro, in that cultured keratinocytes expressed significant levels of IL-21R, whereas no signal was observed in fibroblasts. Interestingly, mRNA for IL-21 could not be detected by real-time PCR and in situ hybridization. Various concentrations of key cytokines in the pathogenesis of SSc did not stimulate the expression of IL-21R mRNA in cultured keratinocytes and dermal fibroblasts. In the SCID mouse transplantation model, the overexpression of IL-21R mRNA in SSc keratinocytes remained unchanged after transplantation. CONCLUSION: The up-regulation of IL-21R in keratinocytes indicates that, similar to fibroblasts and endothelial cells, the expression pattern is altered in SSc. Moreover, the expression of IL-21R appears to be independent of key cytokines that are operant in SSc.

Adolescent↗

PubMed2005

Cyclooxygenase- and lipoxygenase-derived eicosanoids in bronchoalveolar lavage fluid from patients with scleroderma lung disease: an imbalance between proinflammatory and antiinflammatory lipid mediators.

OBJECTIVE: Eicosanoids play a key role in the regulation of inflammation and fibrosis. Recently we showed that levels of 5-lipoxygenase (5-LOX)-derived proinflammatory/profibrotic leukotrienes are elevated in bronchoalveolar lavage (BAL) fluid from patients with scleroderma lung disease (SLD). The present study was undertaken to investigate whether increased levels of leukotrienes are balanced by the antiinflammatory/antifibrotic cyclooxygenase (COX)- and 15-LOX-derived eicosanoids in the lungs of patients with SLD. METHODS: Levels of 5-LOX-derived leukotriene B(4) (LTB(4)), COX-derived prostaglandin E(2) (PGE(2)), and 15-LOX-derived 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxin A(4) (LXA(4)) in BAL fluid from systemic sclerosis (SSc) patients with SLD (n = 32) and without SLD (n = 16) and from healthy individuals (n = 12) were measured by enzyme-linked immunosorbent assay. RESULTS: Levels of LTB(4) (mean +/- SEM 248 +/- 29 pg/ml) and PGE(2) (51 +/- 10 pg/ml) in SSc patients with SLD were significantly higher compared with patients without SLD (LTB(4) 119 +/- 35 pg/ml, PGE(2) 17 +/- 3 pg/ml; P < 0.05 for both) and with healthy controls (85 +/- 12 pg/ml and 19 +/- 2 pg/ml, respectively; P < 0.05 for both). Accordingly, the mean +/- SEM PGE(2):LTB(4) ratio was similar in SSc patients with SLD (0.30 +/- 0.05), SSc patients without SLD (0.29 +/- 0.07), and controls (0.31 +/- 0.07). In contrast, levels of 15-HETE and LXA(4) in patients with SLD did not differ significantly from levels in patients without SLD or in controls. The ratio of LXA(4):LTB(4) in SLD patients (0.16 +/- 0.03) was significantly lower (P < 0.05) than that in patients without SLD (0.40 +/- 0.10) or controls (0.34 +/- 0.08). CONCLUSION: Increased production of LTB(4) in the lungs of patients with SLD is not balanced by an up-regulation of 15-LOX-derived antiinflammatory/antifibrotic eicosanoids such as 15-HETE or LXA(4). Targeting the 5-LOX/15-LOX balance may be of practical value in the treatment of SLD.

Adult↗

PubMed2005

[Capillaroscopy in the diagnosis of systemic sclerosis].

Capillaroscopy is a safe, simple, non-invasive, low-cost analysis of the nailfold circulation. Vascular lesions play a significant role in the pathogenesis of systemic sclerosis. It has been shown that a characteristic microangiopathy, so-called "scleroderma pattern capillary abnormalities", --are present in the majority of patients with systemic sclerosis and already appear in the early stage of the disease. Due to this fact, capillarosopy is considered a practical tool for diagnosing and monitoring patients with systemic sclerosis. Capillaroscopy can help in the selection of patients that need more aggressive therapeutic interventions. Recently, the presence of typical capillaroscopic abnormalities has been suggested as one of the minor criteria for the early diagnosis and classification of systemic sclerosis. The present study presents the role of capillaroscopy in the management of patients with systemic sclerosis.

Diagnosis, Differential↗

PubMed2005

[Immunopathological disturbances in systemic sclerosis].

Systemic sclerosis (SSc) is a disorder of the connective tissue characterized by the vascular dysfunction and progressive fibrosis of the skin, and various internal organs, which results in their dysfunction and failure. Activation of the immune system seems to play an important role in the pathogenesis of the disease. Contribution of the immune mechanisms to the development of the disease is indicated by the presence of the typical auto-antibodies, inflammatory cells infiltration in the skin and internal organs, and activation of cells participating in the immune response. Activation of the immune cells leads to release of proinflammatory/profibrotic cytokines and growth factors which in turn stimulate extensive proliferation of fibroblasts and collagen production. Activation of the immune system may also lead to impairment of endothelial function and development of angiopathy typical for systemic sclerosis, and subsequently chronic ischaemia of the affected tissues. In this review we describe the abnormalities of endothelial cells, T and B cells, and fibroblasts in patients with systemic sclerosis.

Autoantibodies↗

PubMed2005

[An up date on pulmonary hypertension related to systemic sclerosis].

Systemic sclerosis (scleroderma) is a chronic, progressive connective tissue disease characterized by typical skin changes and internal organ involvement. Arterial pulmonary hypertension is found in approximately 10-15% of patients with systemic sclerosis, and is considered as one of the most fatal complications of the disease. When pulmonary hypertension secondary to scleroderma related interstitial lung disease, left-sided cardiac insufficiency and thrombo-embolic disease is also taken into account, the frequency of pulmonary hypertension in systemic sclerosis may be as high as.50%. Recent investigations brought new information considering the pathogenesis of pulmoanry hypertension and allowed new therapeutic approches to be introduced. Early diagnosis of pulmonary hypertension is a key issue in clinical practice, but it is a challange in patients with systemic disease such as systemic sclerosis. Current review presents up to date information on the pathogenesis, early diagnosis and treatment of pulmonary hypertension related to systemic sclerosis.

Humans↗

PubMed2005

[Interstitial lung disease related to systemic connective tissue diseases].

Interstitial lung disease (ILD) is one of the most frequent and most serious complications of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, dermato- and polymyositis, Sjogren's syndrome, or mixed connective tissue disease. Diagnosis of ILD is often delayed in patients with connective tissue diseases because of the systemic character of the primary condition, restricted physical activity of the patient and insufficient awareness of the physycian. The aim of the current review is to present the up-to-date information on ethiopathology, classification, diagnosis and treatment of ILD in patients with connective tissue diseases.

Collagen Diseases↗

PubMed2003

Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage fluid from patients with scleroderma lung disease.

OBJECTIVE: The leukotrienes are a family of arachidonic acid-derived lipid mediators with proinflammatory and profibrotic properties. The aim of this study was to analyze the role of leukotriene B(4) (LTB(4)) and LTE(4) in the pathogenesis of scleroderma lung disease (SLD). METHODS: Nineteen systemic sclerosis (SSc) patients with SLD, 11 SSc patients without SLD, and 10 healthy controls were studied. Bronchoalveolar lavage (BAL) fluid was obtained during routine bronchoscopy of the right middle lobe in all study subjects. Levels of LTB(4) and LTE(4) were measured using enzyme immunoassay kits. RESULTS: Levels of LTB(4) and LTE(4) were significantly higher in SSc patients with SLD (251 +/- 170 pg/ml and 479 +/- 301 pg/ml, respectively), than those in patients without SLD (114 +/- 86 and 159 +/- 149 pg/ml) and those in normal controls (86 +/- 49 and 110 +/- 67 pg/ml). In the total group of patients with SSc, levels of both leukotrienes correlated positively with the total number of cells in the BAL fluid and correlated negatively with the forced vital capacity. After intravenous pulse therapy with cyclophosphamide in 6 patients, there was a significant reduction in the concentration of LTB(4) (from 380 +/- 196 pg/ml to 155 +/- 123 pg/ml) but no significant difference in the levels of LTE(4) (from 697 +/- 325 pg/ml to 418 +/- 140 pg/ml). CONCLUSION: Our findings show that LTB(4) and LTE(4) levels are elevated in SSc patients with SLD and correlate with parameters of inflammation in the lungs. These results indicate that leukotrienes may contribute to the pathogenesis of SLD and may represent a new therapeutic target.

Adult↗