Dataset Information

Differential regulation of cathepsin S and cathepsin L in interferon gamma-treated macrophages.

ABSTRACT: Cathepsin S (catS) and cathepsin L (catL) mediate late stages of invariant chain (Ii) degradation in discrete antigen-presenting cell types. Macrophages (Mphis) are unique in that they express both proteases and here we sought to determine the relative contribution of each enzyme. We observe that catL plays no significant role in Ii cleavage in interferon (IFN)-gamma-stimulated Mphis. In addition, our studies show that the level of catL activity is significantly decreased in Mphis cultured in the presence of IFN-gamma whereas catS activity increases. The decrease in catL activity upon cytokine treatment occurs despite the persistence of high levels of mature catL protein, suggesting that a specific inhibitor of the enzyme is up-regulated in IFN-gamma-stimulated peritoneal Mphis. Similar inhibition of activity is observed in dendritic cells engineered to overexpress catL. Such enzymatic inhibition in Mphis exhibits only partial dependence upon Ii and therefore, other mechanisms of catL inhibition are regulated by IFN-gamma. Thus, during a T helper cell type 1 immune response catL inhibition in Mphis results in preferential usage of catS, such that major histocompatibility complex class II presentation by all bone marrow-derived antigen-presenting cell is regulated by catS.

SUBMITTER: Beers C

PROVIDER: S-EPMC2193812 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

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Publications

Differential regulation of cathepsin S and cathepsin L in interferon gamma-treated macrophages.

Beers Courtney C Honey Karen K Fink Susan S Forbush Katherine K Rudensky Alexander A

The Journal of experimental medicine 20030101 2

Cathepsin S (catS) and cathepsin L (catL) mediate late stages of invariant chain (Ii) degradation in discrete antigen-presenting cell types. Macrophages (Mphis) are unique in that they express both proteases and here we sought to determine the relative contribution of each enzyme. We observe that catL plays no significant role in Ii cleavage in interferon (IFN)-gamma-stimulated Mphis. In addition, our studies show that the level of catL activity is significantly decreased in Mphis cultured in th ...[more]

PMID: 12538657

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Project description:Previous studies have shown that interferon-mediated antiviral activity is subtype-dependent. Using a whole transcriptome procedure, we aimed to characterize the small RNA transcriptome (sRNA-Seq) and specifically the differential microRNA (miRNA) responses in porcine alveolar macrophages (PAMs) upon antiviral activation during viral infection and interferon (IFN) stimulation. Data showed that near 90% of the qualified reads of sRNA were miRNAs, and about 10% of the other sRNAs included rRNA, snoRNA, snRNA, and tRNA in order of enrichment. As the majority of sRNA (>98%) were commonly detected in all PAM samples under different treatments, about 2% sRNA were differentially expressed between the different antiviral treatments. Focusing on miRNA, 386 miRNA were profiled, including 331 known and 55 novel miRNA sequences, of which most were ascribed to miRNA families conserved among vertebrates, particularly mammalian species. Of the miRNA profiles comparably generated across the different treatments, in general, significantly differentially expressed miRNA (SEM) demonstrated that: (1) the wild-type and vaccine strains of a porcine arterivirus (a.k.a., PRRSV) induced nearly reversed patterns of up- or down-regulated SEMs; (2) similar SEM patterns were found among the treatments by the vaccine strain and antiviral IFN-α1/-ω5 subtypes; and (3) the weak antiviral IFN-ω1, however, remarked a suppressive SEM pattern as to SEMs upregulated in the antiviral treatments by the vaccine and IFN-α1/-ω5 subtypes. Further articulation identified SEMs commonly or uniquely expressed in different treatments, and experimentally validated that some SEMs including miR-10b and particularly miR-9-1 acted significantly in regulation of differential antiviral reactions stimulated by different IFN subtypes. Therefore, this study provides a general picture of porcine sRNA composition and pinpoints key SEMs underlying antiviral regulation in PAMs correlated to a typical respiratory RNA virus in pigs.

Dataset Information

Differential regulation of cathepsin S and cathepsin L in interferon gamma-treated macrophages.

Publications

Differential regulation of cathepsin S and cathepsin L in interferon gamma-treated macrophages.

Similar Datasets

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