IFN Regulatory Factor-1 Regulates IFN-γ-Dependent Cathepsin S Expression

Gravesande, Karin Storm van’s; Layne, Matthew D.; Ye, Qiang; Le, Louis; Baron, Rebecca M.; Perrella, Mark A.; Santambrogio, Laura; Silverman, Eric S.; Riese, Richard J.

doi:10.4049/jimmunol.168.9.4488

Cited by 76 publications

(81 citation statements)

References 39 publications

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“…3 a-b). Cat S was detected only in the lysosomes of stimulated cells, confirming that INF-␥ induction of human Cat S is not mediated through CIITA (27). Because most lysosomal cathepsins seem to be relatively insensitive to CIITA expression and͞or INF-␥ stimulation, we also investigated the fate of AEP, which is involved in antigen degradation (28).…”

Section: Ii-p10 Accumulates In Hela Cells Transfected With Ciita and mentioning

confidence: 97%

“…Transcription levels were found identical in the parental HeLa cell line and the HeLa-CIITA, as well as the MelJuSo cells. Among all cysteine proteases tested, the transcript for Cat S was the only one not to be detectable by PCR, but Cat S transcription is strongly induced in both INF-␥-treated HeLa-CIITA and MelJuSo cells (27).…”

Section: Ii-p10 Accumulates In Hela Cells Transfected With Ciita and mentioning

confidence: 99%

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Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs

Bania

Gatti

Lelouard

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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MHC class II-restricted antigen presentation plays a central role in the immune response against exogenous antigens. The association of invariant (Ii) chain with MHC class II dimers is required for proper antigen presentation to CD4 ؉ T cells by antigen-presenting cells. MHC class II complexes first traffic through the endocytic pathway to allow Ii chain degradation and antigenic peptide loading before their arrival at the cell surface. In recent years, a considerable effort has been directed toward the identification of proteases responsible for Ii chain degradation. Targeted gene deletion in mice has allowed a precise description of the cysteine proteases involved in the last step of Ii chain degradation. By using nonspecialized cellular models expressing MHC II molecules, we are now exploring the contribution of known cysteine proteases to human Ii chain processing. Surprisingly and contrary to the situation in mouse, cathepsin S was found to be the only human cysteine protease able to efficiently degrade the Ii-p10 fragment in epithelial cells. This selectivity has implications for thymic selection and indicates that differences between man and mice are probably more profound at this level than expected.antigen presentation ͉ lysosome ͉ protease

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Section: Ii-p10 Accumulates In Hela Cells Transfected With Ciita and mentioning

confidence: 97%

Section: Ii-p10 Accumulates In Hela Cells Transfected With Ciita and mentioning

confidence: 99%

Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs

Bania

Gatti

Lelouard

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, analysis of the CTSS promoter region reveals the existence of several consensus binding sites for PU.1, with at least two of these sites located near the CTSS promoter ISRE (6). Based on these observations, we postulated that PU.1 may participate in the transcriptional regulation of CTSS expression in professional APCs, and that this may involve protein-protein interactions with IRF family members.…”

Section: Athepsin S (Ctss)mentioning

confidence: 97%

“…An 892-bp fragment of the CTSS gene (CTSS Ϫ859/ϩ32) was cloned into PGL2 basic (Promega) as previously described (6). CTSS (Ϫ859/ϩ32) was used as a template to generate truncated CTSS 5Ј-flanking regions by PCR, designated CTSS (Ϫ422/ϩ32), CTSS (Ϫ230/ϩ32), and CTSS (Ϫ75/ϩ32).…”

Section: Plasmids and Transient Transfection Analysismentioning

confidence: 99%

PU.1 Regulates Cathepsin S Expression in Professional APCs

Wang

Baron

Zhu

et al. 2006

The Journal of Immunology

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Cathepsin S (CTSS) is a cysteine protease that is constitutively expressed in APCs and mediates processing of MHC class II-associated invariant chain. CTSS and the Ets family transcription factor PU.1 are highly expressed in cells of both myeloid (macrophages and dendritic cells) and lymphoid (B lymphocytes) lineages. Therefore, we hypothesized that PU.1 participates in the transcriptional regulation of CTSS in these cells. In A549 cells (a human epithelial cell line that does not express either CTSS or PU.1), the expression of PU.1 enhances CTSS promoter activity ∼5- to 10-fold. In RAW cells (a murine macrophage-like cell line that constitutively expresses both CTSS and PU.1), the expression of a dominant-negative PU.1 protein and a short-interfering RNA PU.1 construct attenuates basal CTSS promoter activity, mRNA levels, and protein expression. EMSAs show binding of PU.1 to oligonucleotides derived from the CTSS promoter at two different Ets consensus binding elements. Mutation of these sites decreases the baseline CTSS activity in RAW cells that constitutively express PU.1. Chromatin immunoprecipitation experiments show binding of PU.1 with the CTSS promoter in this same region. Finally, the expression of PU.1, in concert with several members of the IFN regulatory factor family, enhances CTSS promoter activity beyond that achieved by PU.1 alone. These data indicate that PU.1 participates in the regulation of CTSS transcription in APCs. Thus, manipulation of PU.1 expression may directly alter the endosomal proteolytic environment in these cells.

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“…However, it is known that CatS promoter activity is mediated by IRF1 binding to a single IRSE site 100 bp upstream from the transcriptional start site of the CatS promoter, and IFN-g treatment has been shown to enhance the affinity of IRF1 to CatS IRSE oligonucleotides. 17 In this study, radiation induced IRF1, which were in turn mediated by ROS-IFN-g pathways and directly involved in CatS promoter activity (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

Radiation‐induced cathepsin S is involved in radioresistance

Seo

Bae

Lee

2009

Intl Journal of Cancer

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Previous studies have suggested that the production of cathepsin S (CatS), a cysteine protease, was specifically induced in radiationinduced rat mammary tumors. In this study, we further investigate the mechanism by which CatS is induced by radiation and its function. Radiation induced production of CatS at both the mRNA and protein level, and increased its protease activity. In addition, these radiation induced changes occurred in a dose and time-dependent fashion. Agents such as bleomycin, As 2 O 3 and H 2 O 2 , which produce reactive oxygen species (ROS), also induced CatS expression; however, other agents that damage DNA such as taxol and cisplatin did not. Additionally, treatment of the cells with the ROS scavengers, N-acetylcysteine and catalase, inhibited the radiation induced CatS expression. Furthermore, radiationinduced ROS was also involved in IFN-c production, which was responsible for radiation-mediated CatS expression. Moreover, electrophoretic mobility shift assay (EMSA) data obtained using an IFN-stimulated response element (ISRE) oligonucleotide revealed that IFN regulatory factor-1 (IRF1) was the critical transcriptional mediator of IFN-c-dependent CatS production after radiation. Finally, CatS overespression was found to induce radioresistance; however, knockdown of CatS resulted in the suppression of radioresistance. Taken together, the results of this study indicate that radiation induced CatS expression via ROS-IFN-c pathways, and that this increased expression may be involved in radioresistance.

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IFN Regulatory Factor-1 Regulates IFN-γ-Dependent Cathepsin S Expression

Cited by 76 publications

References 39 publications

Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs

Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs

PU.1 Regulates Cathepsin S Expression in Professional APCs

Radiation‐induced cathepsin S is involved in radioresistance

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