ovalbumin and zinc-chloride

Zinc oxide nanoparticles (ZnO NPs) have been widely used in industry. The metal composition of PM2.5 might contribute to the higher prevalence of asthma. To investigate the effects of ZnO NPs on allergic airway inflammation, mice were first exposed to different concentrations of ZnO NPs (0.1 mg/kg, 0.5 mg/kg) or to a combination of ZnO NPs and chicken egg ovalbumin (OVA) by oropharyngeal aspiration on day 0 and day 7 and then were sacrificed 5 days later. The subsequent time course of airway inflammation in the mice after ZnO NPs exposure was evaluated on days 1, 7, and 14. To further determine the role of zinc ions, ZnCl2 was also administered. The inflammatory cell count, cytokine levels in the bronchoalveolar lavage fluid (BALF), and lung histopathology were examined. We found significant neutrophilia after exposure to high-dose ZnO NPs on day 1 and significant eosinophilia in the BALF at 7 days. However, the expression levels of the T helper 2 (Th2) cytokines IL-4, IL-5, and IL-13 increased significantly after 24h of exposure to only ZnO NPs and then decreased gradually. These results suggested that ZnO NPs could cause eosinophilic airway inflammation in the absence of allergens.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Chickens; Chlorides; Dose-Response Relationship, Drug; Eosinophils; Female; Immunoglobulin E; Inflammation; Lung; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Ovalbumin; Ovum; Particulate Matter; Th2 Cells; Zinc Compounds; Zinc Oxide

Lead (Pb) is known to preferentially suppress the activation and development of type-1 CD4+ helper T cell (Th1) responses, whereas it enhances the development of type-2 CD4+ helper T cell (Th2) responses. The inhibition of interferon-gamma (IFNgamma) production has been demonstrated in vitro with a Th1 clone and DO11.10 ovalbumin-transgenic (OVA-tg) CD4+ T cells, and in vivo with wild-type and OVA-tg BALB/c mice; however, the mechanisms responsible for the Pb-induced downregulation of IFNgamma have not been reported. Here, we assessed the modulation of IFNgamma production at the mRNA and protein levels. Pb did not significantly affect IFNgamma mRNA expression by a Th1 clone or activated splenocytes, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), ribonuclease protection, and real-time RT-PCR. However, Pb did significantly lower the amount of IFNgamma protein in supernatants and cell lysates of antigen-activated T cells in comparison to stimulated controls, suggesting that the lower amounts of IFNgamma released into culture supernatants were not due to a blockage of secretion that gave rise to a cytoplasmic accumulation of IFNgamma. Pb inhibition also was not prevented by addition of zinc or iron. Pb did not enhance protein degradation of IFNgamma, in that lactacystin, an effective blocker of proteosomal proteolysis, did not prevent loss of IFNgamma; additionally, Pb did not accelerate loss of IFNgamma after cycloheximide treatment. Pb did, however, significantly suppress IFNgamma biosynthesis, as investigated using 35S-incorporation in pulse/chase experiments, although it did not suppress total protein synthesis, indicating that Pb selectively inhibits IFNgamma biosynthesis. Thus, Pb appears to selectively interfere with the translation of certain proteins, such as IFNgamma. IL-12 blocked Pb's preferential promotion of Th2 cells, but absence of STAT6 did not prevent the Pb skewing. Thus, Pb may modulate unique regulatory pathways.

Topics: Animals; Cell Line; Chlorides; Down-Regulation; Ferrous Compounds; Immunity, Cellular; Immunity, Innate; Interferon-gamma; Interleukin-12; Interleukin-4; Lead; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Proteasome Endopeptidase Complex; Protein Biosynthesis; RNA Processing, Post-Transcriptional; RNA, Messenger; Spleen; STAT4 Transcription Factor; STAT6 Transcription Factor; Th1 Cells; Th2 Cells; Time Factors; Zinc Compounds