Serum Levels of TGF-β1 and MCP-1 as Biomarkers for Progressive Coal Workers’ Pneumoconiosis in Retired Coal Workers: A Three-year Follow-up Study

Transforming growth factor-beta (TGF-beta) can regulate cell growth and differentiation as well as production of extracellular matrix proteins. Elevated production of TGF-beta has been associated with human and rodent chronic inflammatory and fibrotic diseases. Using immunohistochemical staining, we have examined lung sections of patients with advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by chronic inflammation and fibrosis and demonstrated a marked and consistent increase in TGF-beta production in epithelial cells and macrophages when compared to patients with nonspecific inflammation and those with no inflammation or fibrosis. In patients with advanced IPF, intracellular staining with anti-LC (1-30) TGF-beta antibody was seen prominently in bronchiolar epithelial cells. In addition, epithelial cells of honeycomb cysts and hyperplastic type II pneumocytes stained intensely. Anti-CC (1-30) TGF-beta antibody, which reacts with extracellular TGF-beta, was localized in the lamina propria of bronchioles and in subepithelial regions of honeycomb cysts in areas of dense fibroconnective tissue deposition. The close association of subepithelial TGF-beta to the intracellular form in advanced IPF suggests that TGF-beta was produced and secreted primarily by epithelial cells. Because of the well-known effects of TGF-beta on extracellular matrix formation and on epithelial cell differentiation, the increased production of TGF-beta in advanced IPF may be pathogenic to the pulmonary fibrotic and regenerative responses seen in this disease.

We tested the power of tumor necrosis factor (TNF)-alpha and/or leptin in predicting the degree of liver involvement in children with nonalcoholic fatty liver disease (NAFLD). We measured serum levels of TNF-alpha and leptin and computed NAFLD activity score (NAS) (NAS >or= 5, diagnostic of nonalcoholic steatohepatitis [NASH]) in 72 consecutive biopsy-proven NAFLD cases (training and validation sets, 36 cases each). Univariate analysis evaluated variables significantly associated with a diagnostic NAS. Receiver operating characteristic (ROC) curve analysis assessed the diagnostic value of selected variables in predicting a NAS of 5 or more.TNF-alpha (P < .0001), leptin (P = .001); triglycerides (P = .013), and alkaline phosphatase (P = .046) levels were significantly associated with a NAS of 5 or more. TNF-alpha and leptin levels predicted the risk of NAS of 5 or more. ROC analyses defined cutoff values for TNF-alpha, leptin, and risk score. They identified 90%, 83%, and 83% of the cases, respectively, with a NAS of 5 or more (true-positive cases) from the validation set.TNF-alpha alone or combined with leptin in a simple risk score can accurately predict a NAS of 5 or more. TNF-alpha seems to be a specific laboratory marker of NASH.

Human peripheral blood monocytes and neutrophils secrete TGF-beta. Activation of monocytes with LPS stimulates the secretion of TGF-beta; however, the production of TGF-beta by neutrophils was not altered by treatment with LPS. The secreted TGF-beta appears to be in a fully active form since acid treatment of the conditioned medium does not increase the amount of TGF-beta activity. TGF-beta 1 transcripts were detected at similar levels in both activated and nonactivated monocytes and neutrophils, suggesting that the increase in TGF-beta secretion after activation of monocytes is regulated by a posttranscriptional mechanism. Western blot analysis with anti-N-terminal TGF-beta 1 peptide antibodies indicate the leukocyte-derived TGF-beta is beta 1. In addition, TGF-beta 1 transcripts were detected in rat peritoneal macrophages and in a differentiating human hematopoietic tumor cell line (HEL). The ability of inflammatory cells such as monocytes and neutrophils to produce TGF-beta may play an important role in the function of these cells in wound repair, in the immune response, and in the pathogenesis of fibrotic diseases.