Ng could promote collagen deposition around bronchi on P150. In addition, the transcriptional levels of CTGF and TGF-b1, which are important mediators of fibrosis and organ remodeling, were significantly upregulated in neonatal overfeeding mice on P150. Therefore, our data suggested that neonatal overfeeding induced obesity may be a potential risk for lung fibrosis, which is related to inflammatory cytokine (TNF-a and TGF-b1) released by increased macrophages. In summary, our study suggests that neonatal overfeeding could increase pulmonary disease susceptibility by enhancing airway hyperresponsiveness and lung inflammation. It is plausible that the resulting airway hyperresponsiveness, lung inflammation and remodeling observed in these obese mice are the consequence of overproduction of inflammatory Autophagy cytokines secreted from the active macrophages in the lung. Future studies will examine airway responsiveness after inflammatory stimuli and determine whether food restriction is sufficient to improve metabolic and respiratory phenotypes of these neonatal overfeeding mice.Neonatal Overfeeding and Airway ResponsivenessFigure 6. Neonatal overfeeding induces lung fibrosis on P150. The lungs were subjected to Masson staining (A) and a-SAM immunohistochemistry (B) for collagen in peri-bronchiolar areas on P21 and P150. Masson positive staining was blue and a-SAM positive staining was brown-reddish. The mRNA levels of TGF-b1 (C) and CTGF (D) in lungs were measured by quantitative real-time PCR. Data were expressed as mean6 SEM, and the significant difference between two groups was analyzed by Student t-tests, *P,0.05. doi:10.1371/journal.pone.0047013.gAuthor ContributionsConceived and designed the experiments: XX YH. Performed the experiments: ZY DL XC DW DH LZ. Analyzed the data: ZY XX.Contributed reagents/materials/analysis tools: XX YH. Wrote the paper: ZY XX YH.
Chronic infection with Hepatitis C virus (cHCV) is present in 3 of the world’s population with prevalence ranging from 0.1?5 in different European countries [1]. HCV is currently treated with a combination of interferon alpha and ribavirin, however a sustained virological response (SVR) is achieved only in ,50 of cases [1,2]. More recently IFN-lambda (IFN-l) has emerged as a potential new therapeutic option for HCV infection. Elevated IFN- l transcripts were identified in the livers and in the peripheral blood mononuclear cells (PBMCs) of patients with cHCV [3,4]. In vitro IFN- l is a potent inhibitor of HCV replication [4,5]. Preclinical and early clinical data indicated that IFN- l was well tolerated in animals and presented minimal sideeffects. [6]. Further, genetic variations in IFN- l genes may predict sustained virological response (SVR) to standard therapy [7]. The IFN- l class includes 3 cytokines, IL-29 (IFN- l 1), Autophagy IL-28A (IFN- l 2), and IL-28B (IFN- l3), which are produced upon stimulation with viruses or certain Toll-like receptor ligands mostly by 12926553 hepatocytes, epithelial cells, and to a lesser extent by immune cells [5,8,9]. All IFN- 
l class cytokines employ a common IFN- l heterodimer receptor composed of a unique IFN- l R1 chain and an IL-10R2 
chain, the latter is also used by other cytokine receptors [8]. The signaling events downstream of IFN- l R are shared with IFN-aR and include activation of STAT1, STAT2, and IRF9, all leading to induction of interferon-stimulated genes and antiviral activity. Taking into account that IFN- l polymorphisms are associated with both.Ng could promote collagen deposition around bronchi on P150. In addition, the transcriptional levels of CTGF and TGF-b1, which are important mediators of fibrosis and organ remodeling, were significantly upregulated in neonatal overfeeding mice on P150. Therefore, our data suggested that neonatal overfeeding induced obesity may be a potential risk for lung fibrosis, which is related to inflammatory cytokine (TNF-a and TGF-b1) released by increased macrophages. In summary, our study suggests that neonatal overfeeding could increase pulmonary disease susceptibility by enhancing airway hyperresponsiveness and lung inflammation. It is plausible that the resulting airway hyperresponsiveness, lung inflammation and remodeling observed in these obese mice are the consequence of overproduction of inflammatory cytokines secreted from the active macrophages in the lung. Future studies will examine airway responsiveness after inflammatory stimuli and determine whether food restriction is sufficient to improve metabolic and respiratory phenotypes of these neonatal overfeeding mice.Neonatal Overfeeding and Airway ResponsivenessFigure 6. Neonatal overfeeding induces lung fibrosis on P150. The lungs were subjected to Masson staining (A) and a-SAM immunohistochemistry (B) for collagen in peri-bronchiolar areas on P21 and P150. Masson positive staining was blue and a-SAM positive staining was brown-reddish. The mRNA levels of TGF-b1 (C) and CTGF (D) in lungs were measured by quantitative real-time PCR. Data were expressed as mean6 SEM, and the significant difference between two groups was analyzed by Student t-tests, *P,0.05. doi:10.1371/journal.pone.0047013.gAuthor ContributionsConceived and designed the experiments: XX YH. Performed the experiments: ZY DL XC DW DH LZ. Analyzed the data: ZY XX.Contributed reagents/materials/analysis tools: XX YH. Wrote the paper: ZY XX YH.
Chronic infection with Hepatitis C virus (cHCV) is present in 3 of the world’s population with prevalence ranging from 0.1?5 in different European countries [1]. HCV is currently treated with a combination of interferon alpha and ribavirin, however a sustained virological response (SVR) is achieved only in ,50 of cases [1,2]. More recently IFN-lambda (IFN-l) has emerged as a potential new therapeutic option for HCV infection. Elevated IFN- l transcripts were identified in the livers and in the peripheral blood mononuclear cells (PBMCs) of patients with cHCV [3,4]. In vitro IFN- l is a potent inhibitor of HCV replication [4,5]. Preclinical and early clinical data indicated that IFN- l was well tolerated in animals and presented minimal sideeffects. [6]. Further, genetic variations in IFN- l genes may predict sustained virological response (SVR) to standard therapy [7]. The IFN- l class includes 3 cytokines, IL-29 (IFN- l 1), IL-28A (IFN- l 2), and IL-28B (IFN- l3), which are produced upon stimulation with viruses or certain Toll-like receptor ligands mostly by 12926553 hepatocytes, epithelial cells, and to a lesser extent by immune cells [5,8,9]. All IFN- l class cytokines employ a common IFN- l heterodimer receptor composed of a unique IFN- l R1 chain and an IL-10R2 chain, the latter is also used by other cytokine receptors [8]. The signaling events downstream of IFN- l R are shared with IFN-aR and include activation of STAT1, STAT2, and IRF9, all leading to induction of interferon-stimulated genes and antiviral activity. Taking into account that IFN- l polymorphisms are associated with both.
