Gene expression in bronchoalveolar lavage cells from scleroderma patients.
The hypothesis of this study is that activation of cell-mediated immunity with associated macrophage activation occurs in the lungs of scleroderma patients with lung inflammation. Gene expression profiles were determined in bronchoalveolar lavage (BAL) cells from scleroderma patients with and without lung inflammation and control subjects, using DNA array technology. Enzyme-linked immunosorbent assay was used to measure proteins in BAL fluids. Gene expression profiles were similar in BAL cells from patients without lung inflammation and control subjects. Gene expression profiles in patients with lung inflammation showed increased expression of chemokines and chemokine receptor genes, which would lead to migration of T cells, especially type 2 T cells, and phagocytic cells. Protein levels of pulmonary and activated-response chemokine and monocyte chemoattractant protein-1 were elevated. Other changes in gene expression suggested alterations in gene transcription, cell cycle control, vesicle transport, antigen-presenting function, and intracellular signaling. Two anti-inflammatory cytokines, interleukin-1 receptor antagonist and transforming growth factor-beta1, had increased expression, consistent with other human fibrotic lung diseases and animal models of lung fibrosis. These findings suggest recruitment of T cells and chronic macrophage activation in scleroderma patients at greater risk for lung fibrosis, but differ from typical delayed-type hypersensitivity responses, without prominence of type 1 T cells and inflammatory cytokines.
Luzina
Irina G
IG
Research Service, Veterans Affairs Maryland Health Care System and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Atamas
Sergei P
SP
Wise
Robert
R
Wigley
Fredrick M
FM
Xiao
Hui Qing
HQ
White
Barbara
B
D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D002452:Cell Count; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D020407:Internet; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011014:Pneumonia / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000209:etiology; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D019707:Receptors, Chemokine