Expression of macrophage inflammatory protein-3 beta/CCL19 in pulmonary sarcoidosis.
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.
Gibejova
Agata
A
Department of Immunology, Palacky University, Olomouc, Czech Republic.
Mrazek
Frantisek
F
Subrtova
Daniela
D
Sekerova
Veronika
V
Szotkowska
Jaroslava
J
Kolek
Vitezslav
V
du Bois
Roland M
RM
Petrek
Martin
M
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D016572:Cyclosporine / Q000276:immunology / Q000627:therapeutic use; D003907:Dexamethasone / Q000276:immunology / Q000627:therapeutic use; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
C515460:CCL19 protein, human; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D003907:Dexamethasone; D016572:Cyclosporine