The correlation of the BMP-4 and BMP-7 proteins of the TGFß-BMP-SMAD pathway in the response to a specific and non-specific trigger in asthma.

INTRODUCTION: Asthma is characterized by persistent inflammation, airway hypersensitivity and remodelling. Bone Morphogenetic Proteins belong to the Transforming Growth Factor Superfamily and have a similar signalling transduction pathway and common co-mediating protein. However, the BMPs role in the remodelling remains unclear; they appear to be involved in the airway inflammation and fibrogenesis process. MATERIAL AND METHODS: 60 patients with asthma and 48 healthy volunteers were recruited for the study. Blood samples were collected before, 1 hour, 24 and 48 hours after the allergen or the methacholine challenge test. Evaluation of BMP-4 and BMP-7 serum concentration and expression was performed using ELISA and real time PCR methods, respectively. RESULTS: Statistically significant differences in BMP-7 concentration between healthy controls and asthmatics before the chal-lenge were noted. We found two statistically significant correlations: between the basal BMP-4 concentration and the FEV1(L) raw value and FEV1/FVC(%) index. We did not observe significant changes in the gene expression of BMP-4 and BMP-7 in different time points. CONCLUSIONS: Observed differences in BMP-7 concentration between asthmatic and healthy groups and correlations between BMP-4 concentration and some lung function test values may indicate the role of the BMPs in the etiopathogenesis of asthma. The unique characteristic of our study is the evaluation of BMPs serum levels, not in the bronchial epithelium.

The influence of COVID-19 pandemic lockdown on the physical activity of people with multiple sclerosis. The role of online training.

BACKGROUND: COVID-19 pandemic has affected people with multiple sclerosis (PwMS) on various levels. Pandemic lockdown influenced the access to typical measures of physical activity such as out-door training or gym exercises. METHODS: We performed a survey assessing physical activity during pandemic lockdown among PwMS treated in our MS center. The questionnaire encompassed questions regarding physical activity before and during lockdown, including the employment of online technologies. RESULTS: The survey was completed by 262 PwMS. Physical activity before lockdown was declared by 74.4% of PwMS, regular exercises were declared by 30.9% of participants. Among physically active PwMS 50.5% limited their physical activity during the COVID-19 lockdown. The decrease in physical activity was reported more frequently by PwMS with higher levels of disability, particularly declaring regular exercises before lockdown. In the opinion of 39,7% of PwMS online training could replace standard exercises, however only 19,9% of PwMS were actively looking for online training during the lockdown. The interest in online exercise was greatest in the group ≤30 years of age and EDSS ≤2. Synchronous exercises were the preferred online training, particularly among PwMS with EDSS≥4. CONCLUSION: Our findings indicate a need for systematic educational and organizational measures, promoting physical activity among PwMS and acknowledging pandemic conditions.

Prevalence, risk factors and underdiagnosis of asthma in the general population aged over 60 years.

INTRODUCTION: Bronchial asthma is one of the frequent chronic diseases in elderly persons. Global data show that 6.5-17% of the elderly suffer from asthma. However, there are no Polish data available on asthma prevalence in this group. AIM: This article is a retrospective analysis of the Polish Multicentre Study of Epidemiology of Allergic Diseases (PMSEAD) results aimed at assessing prevalence and clinical characteristics in the elderly. MATERIAL AND METHODS: The study was conducted in 1998-1999 in 11 research centres in Poland, including the Lodz centre. The study included randomly selected subjects of both sexes. Demographics and prevalence were assessed among adults (aged 16-80 years) based on the nationwide database and the detailed clinical analysis was based on the Lodz centre database. RESULTS: Nationwide data were obtained from 12 970 adults, including 1057 respondents in the Lodz Province; 20.3% of respondents in Poland and 23.6% in the Lodz Province were over 60 years of age. In both groups, elderly participants significantly more frequently suffered from asthma (asthma prevalence in this group was 6.7% for Poland and 12.0% for the Lodz Province). The multivariate analysis demonstrated that age over 60 years (OR = 2.08), residence in the city centre (OR = 3.30), and occurrence of seasonal allergic rhinitis (OR = 3.11) were significant risk factors for asthma occurrence among the residents of the Lodz Province. Among the elderly in Lodz, almost 50% of patients with asthma had not had a proper diagnosis made despite reporting clinical symptoms. CONCLUSIONS: In Poland asthma is a common and frequently underdiagnosed disease in the elderly.

Role of IL-15 in the modulation of TGF-ß1-mediated inflammation in asthma.

Transforming growth factor (TGF)-ß1 has an essential role in bronchitis and the induction of bronchial remodelling, which are critical processes in the pathogenesis of asthma. However, the role of interleukin (IL)-15 in asthma inflammation remains unclear. The aim of the present study was to evaluate the effect of TGF-ß1 mRNA expression on IL-15 mRNA expression in asthmatic patients and to assess the role of IL-15 in the clinical course of asthma. The study included 221 participants, comprising 130 patients with asthma and 91 healthy volunteers. The participants were subjected to testing using spirometry, as well as the Asthma Control Test™ and Borg Scale. The expression of TGF-ß1 and IL-15 mRNA was analyzed in blood samples using reverse transcription-quantitative polymerase chain reaction. Statistical analysis indicated that IL-15 and TGF-ß1 mRNA expression each differed significantly between the patient and control groups (P=0.0016 and P=0.033, respectively). A significant correlation was identified between IL-15 expression and TGF-ß1 expression (R=0.41, P=0.0005). No correlation was observed between IL-15 expression and the degree of asthma severity, the results of spirometric examination or the frequency of asthma exacerbations. Further analysis revealed that IL-15 expression was elevated following the administration of inhaled glucocorticosteroids (iGCs; P=0.024), and reduced following methylxanthine treatment (P<0.001). The occurrence of dyspnoea differed between the study and control groups, and this was not found to be associated with IL-15 expression. Since IL-15 expression was correlated with TGF-ß1 expression among asthmatic patients, and IL-15 expression was elevated following iGC administration, the results of the study suggest that IL-15 activity might be associated with the pathogenesis of asthma.

Selected bone morphogenetic proteins - the possibility of their use in the diagnostics and therapy of severe asthma.

Asthma is a chronic heterogeneous illness of the lower airway with an inflammatory basis, developing from hyperresponsiveness and bronchial obstruction. One of the more unfavourable processes occurring in the airway are the long-term changes of the respiratory tract known as remodelling, resulting in complete irreversible obstruction. Bone morphogenetic protein (BMP) is a member of the Transforming Growth Factor beta (TGF-b) superfamily, which regulates processes in embryonic and post-embryonic development. The role played by BMP is regulation of degradation and remodelling of the extracellular matrix, which is one of the elements involved in the reconstruction of the structure of the bronchi in severe asthma. This paper presents the antagonistic properties of BMP against TGF-b, anti-inflammatory and counteracting fibrosis in the respiratory tract. The current state of knowledge indicates that this group of cytokines are potential new markers of remodelling in severe asthma, and further studies on their therapeutic value are necessary.

Serum Cyclophilin A Correlates with Increased Tissue MMP-9 in Patients with Ulcerative Colitis, but Not with Crohn's Disease.

BACKGROUND: Cyclophilin A (CyPA) is an immunomodulatory protein, high expression of which correlates with poor outcome of patients with inflammatory diseases. However, its role in inflammatory bowel disease (IBD) has not been studied. AIM: This study analyzes the correlation between cyclophilin A, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)/MMP-9 complexes in the inflamed and non-inflamed colon mucosa of UC and CD patients. METHODS: Serum and biopsy specimens from inflamed and non-inflamed colonic mucosa of 38 patients with IBD (19 with UC and 19 with CD) and 16 controls were included in our study. We measured serum and tissue level of CyPA, and tissue level of TNF-α, MMP-9, TIMP-1/MMP-9, and TIMP-2/MMP-9 using ELISA method. RESULTS: Our results indicated that serum, but not tissue CyPA is increased in UC, rather than in CD patients, compared to the control. The increase correlated with higher tissue concentration of MMP-9 and TNF-α, especially in the UC group. Moreover, we observed significantly higher level of TIMP-1/MMP-9 in UC and CD group, which overlapped with the change in MMP-9. There was no change in TIMP-2/MMP-9 in the analyzed groups. CONCLUSION: The current study suggests that serum CyPA may be an independent additional marker of IBD, especially of UC. Higher CyPA level may be followed by increased MMP-9 in those patients. However, further studies are necessary to verify the role of CyPA in IBD development.

Identification of Relationships Between Interleukin 15 mRNA and Brain-Derived Neurotrophic Factor II mRNA Levels With Formal Components of Temperament in Asthmatic Patients.

Asthma is a chronic inflammatory and heterogeneous disease developing mostly through allergic inflammation, which modifies the expression of various cytokines and neurotrophins. Previous studies suggest the involvement of interleukin (IL)-15 in the regulation of immune response in asthma. Brain-derived neurotrophic factor (BDNF) II plays an important role as a regulator of development and survival of neurons as well as maintenance of their physiological activity. Chronic stress associated with asthma and elevated IL-15 mRNA and BDNFII mRNA levels may affect the mood and a subjective sensation of dyspnoea-inducing anxiety. Psychopathological variables and numerous cytokine/neurotrophin interactions influence the formation of temperament and strategies of coping with stress. The aim of the study was to identify the role of IL-15 mRNA and BDNFII mRNA expressions and their effect on components of temperament and strategies of coping with stress in asthmatics. A total of 352 subjects (176 healthy volunteers and 176 asthmatic patients) participated in the study. The Formal Characteristic of Behaviour-Temperament Inventory (FCB-TI), Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory, and Borg Rating of Perceived Exertion (RPE) Scale were applied in all the subjects. The expression of IL-15 and BDNFII gene was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Different levels of IL-15 and BDNFII expressions between healthy volunteers and patients were revealed in the study. IL-15 enhanced the BDNFII mRNA expression among patients with bronchial asthma. The depression level negatively correlated with the BDNFII mRNA expression. This neurotrophin modified the temperament variable. BDNFII significantly affected (proportional relationship) the level of briskness in asthmatic patients. BDNFII might influence the level and style of coping with stress (emotion-oriented style). This hypothesis requires further studies on protein functional models. The obtained data confirms the role of IL-15 and BDNFII in the pathomechanisms of depression and formation of selected traits defining the temperament in asthmatics.

The role of the TGF-SMAD signalling pathway in the etiopathogenesis of severe asthma.

Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling.

A novel approach to understanding the role of polymorphic forms of the NR3C1 and TGF-ß1 genes in the modulation of the expression of IL-5 and IL-15 mRNA in asthmatic inflammation.

The aim of the present study was to identify polymorphic forms of the nuclear receptor subfamily 3, group C, member 1 (NR3C1) and transforming growth factor ß1 (TGF-ß1) genes and evaluate their impact on the expression levels of interleukin (IL)-5 and IL­15 in asthma. The study was conducted on a control group consisting of 91 people (54 women and 37 men). The patient group consisted of 130 participants (86 women and 44 men). Genotyping was performed by polymerase chain reaction­restriction fragment length polymorphism (PCR­RFLP) and PCR­high resolution melting (HRM) methods. Interleukin expression was measured by reverse transcription­quantitative polymerase chain reaction. The frequency of the polymorphic forms in the analyzed group were observed to be: Tth111I (rs10052957) controls AA 0.0440, AG 0.5714, GG 0.3846, patients AA 0.1538/AG 0.4692, GG 0.3769; ER22/23EK (rs6189 /rs6190) controls AG 0.0556, GG 0.9444, patients AG 0.0385, GG 0.9615; N363S (rs6195) controls AA 0.6444, AG 0.2667, GG 0.0889, patients AA 0.7846, AG 0.1385, GG 0.0769; BclI (rs41423247) controls CC 0.0879, CG 0.5604, GG 0.3516, patients CC 0.1008, CG 0.5736, GG 0.3256; C­509T (rs1800469) controls TT 0.0805, CT 0.6322, CC 0.2874, patients TT 0.1102, CT 0.5669, CC 0.3228. The results indicated that the C­509T single nucleotide polymorphism (SNP) of the TGF-ß1 gene contributed to an increase in the IL­5 mRNA expression levels. The GG genotype of the N363S SNP of the NR3C1 gene was observed to result in an increase in the expression levels of IL­15. The present study indicated that the selected SNPs of the NR3C1 and TGF­ß1 genes demonstrate a regulatory effect on the expression of IL­5 and IL­15. Therefore, genetic variation affects inflammation in asthma and the clinical course of the disease.

Anti-inflammatory and antinociceptive action of the dimeric enkephalin peptide biphalin in the mouse model of colitis: new potential treatment of abdominal pain associated with inflammatory bowel diseases.

Biphalin, a mixed MOP/DOP agonist, displays a potent antinociceptive activity in numerous animal models of pain. The aim of the study was to characterize the anti-inflammatory and antinociceptive action of biphalin in the mouse models of colitis. The anti-inflammatory effect of biphalin (5mg/kg, twice daily, i.c. and i.p.) was characterized in a semi-chronic mouse model of colitis, induced by i.c. injection of trinitrobenzenesulfonic acid (TNBS). The antinociceptive action of biphalin (5mg/kg, i.p. and i.c.) in inflamed mice was assessed in mustard oil-induced model of visceral pain and in the hot plate test. In the semi-chronic mouse model of colitis, biphalin i.c. (5mg/kg), but not i.p. improved colitis macroscopic score (2.88±0.19 and 4.99±0.80 units for biphalin and vehicle treated animals, respectively). Biphalin injected i.p. and i.c. (5mg/kg) displayed a potent antinociceptive action in the mustard oil-induced pain test. In the hot plate test, biphalin (5mg/kg, i.p.) produced a potent antinociceptive activity in inflamed mice, suggesting central site of action. Our data suggest that biphalin may become a novel opioid-based analgesic agent in IBD therapy and warrant further investigation of its pharmacological profile.