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Tissue fibrosis, a serious and even deadly complication of chronic inflammation and environmental exposures, is regulated by a host of factors including interactions with the extracellular matrix, surface of inflammatory cells, hormones, and an extremely complex and redundant network of profibrotic cytokines. The nature of mechanisms by which cytokines(More)
OBJECTIVE Pulmonary fibrosis is a major cause of death in scleroderma patients. Previous studies have shown an increase in CD8+ T cells in the lungs of scleroderma patients. In the present study, we sought to determine whether activated CD8+ T cells contribute to pulmonary fibrosis in scleroderma patients through the production and activation of profibrotic(More)
Oncostatin M (OSM), an IL-6 family cytokine, has been implicated in a number of biological processes including the induction of inflammation and the modulation of extracellular matrix. In this study, we demonstrate that OSM is up-regulated in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and scleroderma, and investigate the(More)
Studies of IL-4 have revealed a wealth of information on the diverse roles of this cytokine in homeostatic regulation and disease pathogenesis. Recent data suggest that instead of simple linear regulatory pathways, IL-4 drives regulation that is full of alternatives. In addition to the well-known dichotomous regulation of Th cell differentiation by IL-4,(More)
A CC chemokine, CCL18, has been previously reported to stimulate collagen production in pulmonary fibroblasts. This study focused on the role of protein kinase C (PKC) in the profibrotic signaling activated by CCL18 in pulmonary fibroblasts. Of the three PKC isoforms that are predominantly expressed in fibroblasts (PKCalpha, PKCdelta, and PKCepsilon), two(More)
Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that(More)
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(More)
PURPOSE OF REVIEW The triad of pathologic changes that defines systemic sclerosis (scleroderma) includes immune system activation with autoimmunity; an obliterative, proliferative small vessel vasculopathy; and fibrosis. Available data suggest that several cytokines, including chemokines, contribute to the development of scleroderma complications. This(More)
Systemic lupus erythematosus (SLE) is characterized by diverse and complex immune abnormalities. In an effort to begin to characterize the full complexity of immune abnormalities, the expression pattern of 375 potentially relevant genes was analyzed using peripheral blood mononuclear cells (PBMC) from 21 SLE patients and 12 controls by cDNA arrays. When(More)
Levels of pulmonary and activation-regulated chemokine (PARC) mRNA and protein are increased in the lungs of patients with pulmonary fibrosis. The purpose of this study was to establish whether PARC could be directly involved in development of pulmonary fibrosis by stimulating collagen production in lung fibroblasts. Exposure to PARC increased production of(More)