Expression of transforming growth factor beta (TGF-b1) by human preterm lung inflammatory cells.

Using a previously published model of human BPD this study examines whether preterm lung inflammatory cells produce transforming growth factor beta 1 (TGF-beta1), a cytokine pivotal in pathogenesis of bronchopulmonary dysplasia (BPD), and whether TGF-beta1 expression is regulated by inflammation. Lung inflammatory cells (neutrophils and macrophages) recovered in the broncho-alveolar (BAL) fluid of premature infants intubated for respiratory distress after birth expressed TGF-b1 mRNA and protein. Total and bioactive TGF-beta1 were abundantly found in the BAL fluid of the same infants. In cell culture stimulation by lipopolysaccharide (LPS) did not result in any further expression of total or bioactive TGF-beta1 by neonatal lung inflammatory cells over constitutive concentrations. In conclusion, lung inflammatory cells from premature infants are a source of TGF-beta1 but LPS does not regulate TGF-b1 production in these cells.

Expression of transforming growth factor beta (TGF-beta1) in human epithelial alveolar cells: a pro-inflammatory mediator independent pathway.

Regulation of transforming growth factor beta 1 (TGF-beta1) expression remains unclear. Inflammation has been inferred to play a major role in stimulating TGF-beta1 production since high concentrations of TGF-beta1 have been found in the lungs of patients with various diffuse inflammatory lung diseases. To establish an association between inflammation and TGF-beta1 expression, human alveolar epithelial (A549) cells were co-cultured with lipopolysaccharide (LPS), Tumor necrosis factor alpha (TNFalpha), Interleukin 1 beta (IL-1beta) and Interleukin 8 (IL-8) for 12 hours. Total and bioactive TGF-beta1 protein were then measured. A549 cells transiently transfected with a plasmid containing the TGF-beta1 promoter linked to a luciferase reported gene were then co-cultured with the same inflammatory peptides for 12 hours and TGF-beta1 promoter activity determined. Nuclear transcription factors AP-1 (c-jun) or NF-kappa (p65, p50 and p105) were over expressed in A549 cells transiently transfected with the TGF-beta1 promoter and TGF-beta1 promoter activity subsequently measured. Stimulation with inflammatory signals LPS, TNFalpha, IL-1beta, IL-8 resulted in no increase of total or bioactive TGF-beta1 activity above constitutive concentrations in vitro. TGF-beta1 promoter activity was also unchanged from baseline levels in response to the same inflammatory peptides. Expression of c-jun however led to significant increases of TGF-beta1 promoter activity over constitutive levels. In contrast p65 and p105 expression resulted in inhibition of TGF-beta1 promoter activity below baseline levels. We conclude that in a human alveolar epithelial cell line, inflammation does not regulate TGF-beta1 expression. These studies suggest that in lung pathologies such as asthma, lung fibrosis and CLD, TGF-beta1 production may involve pathways independent of inflammatory mediators LPS, TNFalpha, IL-1beta and IL-8.

Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).

Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.

[The serology of toxoplasmosis in uveitis]. / Aspecte ale serologiei toxoplasmozei în uveite.

Determinations for decelerating the antitoxoplasma anticorps that have been effectuated for 696 uveas proved positivity at 123 aerums (17.6%). The repartition of the positive serology concerning the clinic form of the uvea has proved 48 iridocyclitis, 26 serous central corioretinals, 23 in panuveitis, 13 in posterior uveitis, 11 muscular chorioretinitis, 2 in hyalitis. Taking into consideration only the equal or less than 1:160 titrures, these have been at 7 iridocyclitis, 4 serous central chorioretinitis, 4 panuveitis, 3 posterior uveitis and 3 atrophic central chorioretinitis. It is shown that the diagnosis of ocular toxoplasma must be effectuated just corroborating the clinic data with the positive serology. The antiparasitic treatment doesn't influence upon the low titrures of serous anticorps, which generally maintain at the same value all the life.