Transforming growth factor-beta inhibits interferon-gamma-induced HLA-DR expression by cultured human fibroblasts

This study shows the induction of HLA-DR (DR) in fibroblasts by IFN-? and investigates the molecular mechanisms involved in the further DR down-regulation by TGF-?1. Kinetics of DR induction on human dermal fibroblasts by IFN-? showed that 1 hr of exposure was required to induce detectable levels of DR, and maximal DR expression was achieved only after 2 days of exposure to IFN-?. TGF-?1 inhibited DR induction by IFN-?, although complete inhibition never could be achieved, even with high concentrations of TGF-?1 and low concentrations of IFN-?. Inhibition was not accounted for by reduction in cell numbers, as TGF-?1 stimulated growth of the fibroblasts. Inhibition of DR induction was seen only if TGF-?1 was added during the first 24 hr of IFN-? treatment. TGF-?1 inhibited equally well if the cells were pretreated for as little as 1 hr and then washed before addition of IFN-?. TGF-?1 did not cause an overall suppression of protein synthesis. Northern blot analysis revealed that TGF-?1 greatly reduced the steady-state level of DR? mRNA induced by IFN-? at 24 hr, and then DR? transcripts became undetectable at later stages. It is concluded that early intracellular signals must build up to stimulate maximum DR synthesis, which, later on, are inactivated or degraded by the action of TGF-?1. We suggest that these mechanisms regulating DR gene transcription involve the action of genes coding for specific IFN-?-inducible transcriptional factors that are turned on and off in an expeditious manner

The inhibition of NF-kappaB activation pathways and the induction of apoptosis by dithiocarbamates in T cells are blocked by the glutathione precursor N-acetyl-L-cysteine

Nuclear factor-kappaB regulates genes that control immune and inflammatory responses and are involved in the pathogenesis of several diseases, including AIDS and cancer. It has been proposed that reactive oxygen intermediates participate in NF-kappaB activation pathways, and compounds with putative antioxidant activity such as N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) have been used interchangeably to demonstrate this point. We examined their effects, separately and combined, on different stages of the NF-kappaB activation pathway, in primary and in transformed T cells. We show that NAC, contrary to its reported role as an NF-kappaB inhibitor, can actually enhance rather than inhibit IkappaB degradation and, most importantly, show that in all cases NAC exerts a dominant antagonistic effect on PDTC-mediated NF-kappaB inhibition. This was observed at the level of IkappaB degradation, NF-kappaB DNA binding, and HIV-LTR-driven reporter gene expression. NAC also counteracted growth arrest and apoptosis induced by dithiocarbamates. Antagonistic effects were further observed at the level of jun-NH2-terminal kinase, p38 and ATF-2 activation. Our findings argue against the widely accepted assumption that NAC inhibits all NF-kappaB activation pathways and shows that two compounds, previously thought to function through a common inhibitory mechanism, can also have antagonistic effects

Produção, composição e rendimento em queijo do leite de ovelhas Santa Inês tratadas com ocitocina Effects of oxytocin on milk yield and composition of Santa Inês ewes

Objetivou-se avaliar a produção, a composição e o rendimento (na fabricação de queijos) do leite de ovelhas Santa Inês tratadas ou não com ocitocina. Os animais foram mantidos em regime de confinamento e receberam uma dieta com 12% de PB e 65% de NDT. As ovelhas foram distribuídas em dois tratamentos: ordenha manual com injeção endovenosa de três UI de ocitocina e ordenha manual sem injeção de ocitocina (grupo controle). Realizou-se uma ordenha diária, de modo que, até a desmama, as ovelhas permaneceram diariamente com os cordeiros durante 14 horas. Os cordeiros foram desmamados aos 60 dias e as ovelhas continuaram sendo ordenhadas uma vez ao dia até o final da lactação. Foram coletadas amostras de leite para análise dos teores de gordura, de sólidos totais e de sólidos desengordurados. A duração média da lactação foi de 225&plusmn;27,24 e 210&plusmn;38,77 dias para as ovelhas controle e tratadas com ocitocina, respetivamente. Até os 133 dias de lactação, o tratamento com ocitocina (141,63&plusmn;51,52 kg) foi superior ao controle (89,39&plusmn;16,65 kg), entretanto, durante todo o período de lactação, não diferiu (169,64 &plusmn; 71,05) do controle (119,72&plusmn;32,73). As porcentagens de gordura (5,84&plusmn;0,44 e 4,96&plusmn;0,47), sólidos totais (17,40&plusmn;0,42 e 16,18&plusmn;0,57) e sólidos desengordurados (11,57&plusmn;0,15 e 11,22&plusmn;0,25) no leite foram influenciadas pela aplicação de ocitocina. Os resultados revelaram diferença significativa para as ovelhas tratadas com ocitocina, as quais apresentaram maior produtividade e, inclusive, melhor composição química do leite. A aplicação de ocitocina é recomendada para animais não adaptados à rotina de ordenha. O leite das ovelhas Santa Inês apresentou rendimentos de 4,80; 8,29 e 5,99 L/kg para os queijos tipo azeitão, pecorino e roquefort, respectivamente.<br>The objective of this trial was to investigate the effects of oxytocin on milk yield and composition and on cheese yield of Santa Inês sheep receiving a diet containing 12% CP and 65% TDN. Animals were maintained in pens and were assigned to one of the following two treatments: hand milking plus an intravenous injection of 3 IU of oxytocin or hand milking without oxytocin injection (control group). Ewes were milked daily and remained with their lambs for a daily period of 14 hours until weaning; lambs were weaned at 60 days of age and ewes still milked once a day until the end of lactation. Milk samples were collected for analysis of fat, total solids, and solids non-fat. Lactation length averaged 225&plusmn;27.24 and 210&plusmn;38.77 for control and oxytocin-treated ewes, respectively. Ewes receiving oxytocin yielded more milk (141.63&plusmn;51.52 kg) than those on the control group (89.39&plusmn;16.65 kg) until 133 days of lactation; however, total milk yield on the entire lactation did not differ significantly comparing oxyitocin-treated (169.64 &plusmn; 71.05) with control (119.72&plusmn;32.73) animals. Milk contents of fat (5.84&plusmn;0.44 and 4.96&plusmn;0.47), total solids (17.40&plusmn;0.42 and 16.18&plusmn;0.57) and solids non-fat (11.57&plusmn;0.15 and 11.22&plusmn;0.25) differed between both groups of animals, respectively. Results showed improved milk yield and composition on oxytocin-injected ewes; therefore, it is recommended the use of oxytocin to facilitate milk ejection on ewes not adapted to the milking routine. Yields of cheese (L of milk/kg of cheese) averaged 4.80, 8.29 and 5.99 L/kg for azeitão, pecorino, and roquefort cheeses, respectively