Cytokine regulation of pulmonary fibrosis in scleroderma.
Pulmonary fibrosis occurs in up to 70% of scleroderma patients and progresses to cause severe restrictive lung disease in about 15% of patients. The mechanisms that cause pulmonary fibrosis in scleroderma remain incompletely understood. Increased amounts of mRNA or protein for multiple profibrotic cytokines and chemokines have been identified in lung tissue or broncholveolar lavage samples from scleroderma patients, when compared to healthy controls. These cytokines include transforming growth factor (TGF)-beta, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), oncostatin M (OSM), monocyte chemotactic factor-1 and pulmonary and activation-regulated chemokine (PARC). Potential cellular sources of these profibrotic cytokines and chemokines in scleroderma lung disease include alternatively activated macrophages, activated CD8+ T cells, eosinophils, mast cells, epithelial cells and fibroblasts themselves. This review summarizes the literature on involvement of cytokines and chemokines in the development of pulmonary fibrosis in scleroderma.
Atamas
Sergei P
SP
Baltimore VA Medical Center, University of Maryland School of Medicine, Research Service (151), Room 3C-126, 10 North Greene Street, Baltimore, MD 21201, USA. satamas@umaryland.edu
White
Barbara
B
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism*; D027101:DNA Topoisomerase IV / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D045743:Scleroderma, Diffuse / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
C526317:CCN2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; C508351:OSM protein, human; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053683:Oncostatin M; D055513:Connective Tissue Growth Factor; D027101:DNA Topoisomerase IV