Gene Expression in Bronchoalveolar Lavage Cells from Scleroderma Patients

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Abstract
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.