CCL20 protein, human OR C108355 Dotaz Zobrazit nápovědu
In this study, messenger RNA (mRNA) expression for novel T lymphocyte chemoattractants, leukotactin-1, macrophage inflammatory protein (MIP)-3 alpha and MIP-3 beta was investigated in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis, a T cell-mediated disease with typical CD4+ lymphocyte alveolitis. Of these three chemokines, only MIP-3 beta mRNA was upregulated in sarcoidosis, and therefore, protein levels of this chemokine, its pharmacologic regulation, and association with disease clinical course were explored. MIP-3 beta protein concentrations were elevated in BALF from sarcoid patients compared with control subjects (p = 0.001) and in patients with chest X-ray stage II chemokine protein levels were increased compared with stage I (p = 0.003). MIP-3 beta protein was associated predominantly with alveolar macrophages and correlated with BALF lymphocytes and T cell subsets. mRNA expression for the MIP-3 beta receptor, CC chemokine receptor 7, was increased in sarcoidosis and correlated with MIP-3 beta protein levels. MIP-3 beta mRNA and protein expression in BALF cells was suppressed by dexamethasone and cyclosporine A in vitro. In conclusion, MIP-3 beta is implicated in T lymphocyte recruitment in sarcoidosis, is associated with disease progression, and is downregulated by drugs used for sarcoidosis treatment. This novel chemokine, therefore, represents a candidate for studies of sarcoidosis pathobiologic mechanisms.
- MeSH
- aktivace lymfocytů účinky léků imunologie MeSH
- alveolární makrofágy účinky léků imunologie MeSH
- bronchoalveolární lavážní tekutina chemie MeSH
- chemokin CCL19 MeSH
- chemokin CCL20 MeSH
- chemokiny CC analýza genetika imunologie MeSH
- cyklosporin imunologie terapeutické užití MeSH
- dexamethason imunologie terapeutické užití MeSH
- dospělí MeSH
- down regulace účinky léků MeSH
- exprese genu * účinky léků genetika imunologie MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágové zánětlivé proteiny analýza genetika imunologie MeSH
- messenger RNA analýza MeSH
- plicní sarkoidóza krev farmakoterapie imunologie patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- progrese nemoci MeSH
- receptory CCR6 MeSH
- receptory chemokinů * MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- T-lymfocyty účinky léků imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CCL19 protein, human MeSH Prohlížeč
- CCL20 protein, human MeSH Prohlížeč
- CCR6 protein, human MeSH Prohlížeč
- chemokin CCL19 MeSH
- chemokin CCL20 MeSH
- chemokiny CC MeSH
- cyklosporin MeSH
- dexamethason MeSH
- makrofágové zánětlivé proteiny MeSH
- messenger RNA MeSH
- receptory CCR6 MeSH
- receptory chemokinů * MeSH
INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.
- Klíčová slova
- adverse effects of glucocorticoids, autoimmune diseases, blood cell count, cytokine profile, disease activity, long-treated patients, serum protein pattern, systemic inflammation,
- MeSH
- biologické markery krev MeSH
- cytokiny krev MeSH
- dospělí MeSH
- glukokortikoidy * aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu * krev metabolismus MeSH
- revmatoidní artritida * farmakoterapie krev imunologie MeSH
- senioři MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- cytokiny MeSH
- glukokortikoidy * MeSH
- mediátory zánětu * MeSH