thymic-factor--circulating and Adenocarcinoma

Topics: Adenocarcinoma; Animals; Female; Humans; Mammary Neoplasms, Experimental; Mice; Neoplasms, Experimental; Rats; Thymosin; Thymus Hormones

Chorioamnionitis is associated with increased risks of perinatal respiratory failure; however, components of the inflammatory acute-phase response are known to actively promote lung maturation. To manipulate this relationship, we examined the effect of the thymic immunomodulator thymulin on fetal lung mesenchyme-epithelial differentiation during exposure to Escherichia coli lipopolysaccharide (LPS). Gestation day 14 fetal rat lung explants were cultured for 96 h at fetal (23 mmHg) or ambient (142 mmHg) Po(2). Airway surface complexity (ASC, perimeter/ radical area(2)) was greater at fetal vs. ambient Po(2); however, exposure to 0.1-50 microg/ml LPS significantly raised ASC at 2 microg/ml in ambient Po(2) explants. LPS (50 microg/ml) depressed ASC in both conditions to untreated ambient Po(2) control values without changes in necrosis or apoptosis. To manipulate LPS-evoked TNF-alpha and IL-6 release, we exposed explants and A549 cells to combinations of 50 microg/ml LPS, 10 microM ZnCl(2), and 0.1-1,000 ng/ml thymulin at either Po(2). Thymulin+Zn(2+) suppressed and potentiated LPS-evoked TNF-alpha and IL-6 release, yielding an IC(50(TNF-alpha)) of 0.5 +/- 0.01 ng/ml and EC(50(IL-6)) of 1.4 +/- 0.3 ng/ml in A549 cells. This was accompanied by activation of the p38 MAPKMAPKAP-K2 pathway with sustained expression of TNF-alpha and IL-6 transcripts at ambient Po(2). LPS+thymulin+Zn(2+)-treated explants showed proliferation of CCAAT-enhancer binding protein-beta (C/EBPbeta) and fibroblast growth factor-9 immunoreactive mesenchyme, which was abolished by IL-6 antisense oligonucleotides. The posttranscriptional suppression of immunogenic TNF-alpha synthesis coupled with raised IL-6 and C/EBPbeta-dependent mesenchyme proliferation suggests a role for bioactive thymulin in regulating regenerative repair in the fetal lung.

Topics: Adenocarcinoma; Adjuvants, Immunologic; CCAAT-Enhancer-Binding Protein-beta; Cell Differentiation; Cell Division; Cell Line, Tumor; Fetus; Fibroblast Growth Factor 10; Fibroblast Growth Factor 9; Fibroblast Growth Factors; Humans; Hyperplasia; Interleukin-6; Intracellular Signaling Peptides and Proteins; Lipopolysaccharides; Lung; Mesoderm; Oxygen; Protein Serine-Threonine Kinases; Signal Transduction; Thymic Factor, Circulating; Transcription, Genetic; Tumor Necrosis Factor-alpha; Zinc

Conditions for the reproducible measurement of thymic hormonal effect on the functional activity of human peripheral blood lymphocytes (PBL) were determined using a mixed lymphocyte-tumor culture assay. Three thymic hormonal preparations (thymopoietin, thymic humoral factor and TP-1) were tested by this assay and found to have a significant enhancing effect on the blastogenic response. Essential for the demonstration of the hormonal effect was the selection of suboptimal stimulation conditions, with the appropriate cell lines, including the number of stimulating cells and the time in culture. The most reproducible results were achieved when 1 x 10(5) PBL were co-cultured for 4 days with 1 x 10(4) mitomycin-C treated Raji lymphoma cells, after 1 h preincubation with one of the thymic preparations. However, strong enhancing effects of the thymic preparations could also be demonstrated with other tumor cel lines, especially IgR3 melanoma cells.

Topics: Adenocarcinoma; Burkitt Lymphoma; Carcinoma; Cell Line; Cells, Cultured; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Lymphocyte Activation; Lymphocytes; Melanoma; Thymic Factor, Circulating; Thymopoietins; Thymus Extracts; Thymus Hormones; Uterine Neoplasms