Cathepsin S Deficiency Results in Abnormal Accumulation of Autophagosomes in Macrophages and Enhances Ang II–Induced Cardiac Inflammation

Pan, Lili; Li, Yulin; Jia, Lixin; Qin, Yanwen; Qi, Guanming; Cheng, Jizhong; Qi, Yongfen; Li, Huihua; Du, Jie

doi:10.1371/journal.pone.0035315

Cited by 77 publications

(62 citation statements)

References 49 publications

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“…Peritoneal macrophages and neutrophils were obtained by lavaging the peritoneal cavity with 5 ml of 10 mM phosphate-buffered saline (PBS), cells underwent hemocytometry and plating in 6-well plates at 3 ϫ 10 6 cells per well, then culture in DMEM containing 10% fetal bovine serum. After 4 h, non-adherent cells were removed by changing the medium (29). For recombinant C5a treatment, cells were washed with PBS and incubated with recombinant C5a (10 nM) for 6 h.…”

Section: Methodsmentioning

confidence: 99%

Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration

Piao

Cai

Qiu

et al. 2015

Journal of Biological Chemistry

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Background: It is known that the complement system contributes to tumor progression, but the exact mechanism is still unclear. Results: Complement 5a enhances tumor metastasis via monocyte chemoattractant protein-1-mediated inflammatory cell infiltration. Conclusion: Complement 5a plays a pro-metastasis role by establishing an inflammatory microenvironment required for tumor metastasis. Significance: Our results provide a therapeutic insight for complement in treatment of malignant tumors.

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Section: Methodsmentioning

confidence: 99%

Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration

Piao

Cai

Qiu

et al. 2015

Journal of Biological Chemistry

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“…AT1R blockers were shown to decrease the expression of inflammatory cytokines, such as interleukin, 33,34 matrix metalloproteinase, 35 C-reactive protein, 36 and TNF-a 37,38 and to inhibit infiltration of inflammatory cells. 39 Whether losartan reduces inflammation at an early stage after trabeculectomy requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy

Shi

Wang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To examine the effects of losartan on scar formation after trabeculectomy and on fibrotic changes of human Tenon's fibroblasts (HTFs). METHODS.Trabeculectomy was performed on New Zealand rabbits. They were randomized to receive one of the following treatments: 0.9% normal saline, mitomycin-C, or one of the three doses of losartan. Bleb morphology, IOP, and histopathology examination were performed. Primary cultured HTFs were treated with losartan or vehicle, with or without angiotensin II (Ang II). Cell proliferation was assessed by Cell Counting Kit-8 assay, and cell migration was detected by scratch wound and transwell assay. Transdifferentiation was evaluated through the expression of a-smooth muscle actin (a-SMA) by immunofluorescence, real-time PCR, and Western blot. The expression of fibronectin (FN) was evaluated by real-time PCR and Western blot.RESULTS. An amount of 5 mg/mL of losartan subconjunctival injection significantly decreased IOP postoperatively and attenuated wound healing of the filtering bleb in the rabbit model. Immunostaining results showed less myofibroblast and collagen deposition around the bleb area in the losartan-treated eyes. Losartan (10 À5 M) in vitro significantly attenuated Ang II's stimulatory effects on proliferation and migration of HTFs. Expressions of a-SMA and FN in these cells were also decreased by losartan pretreatment.CONCLUSIONS. Losartan attenuates scar formation of filtering bleb after trabeculectomy likely via decreasing proliferation, migration, transdifferentiation, and extracellular matrix deposition of Tenon's fibroblasts. These results indicate that losartan may be an effective therapeutic agent in preventing bleb scar formation and in improving surgical outcome after trabeculectomy.

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“…Cathepsin D and S are two well-characterized endovacuolar asparticand cysteine-type hydrolases, respectively, which are expressed in many cells of the immune system (72). Both hydrolases are known to function as important downstream proteases in autolysosomal/ amphisomal degradation (73,74) in the endovacuolar MHC IIpresentation pathway (75)(76)(77)(78) and are thought to be functionally involved in DCs in the alternative generation of antigenic MHC I peptides (20)(21)(22). In this context, it is interesting to note that autophagosomal processes regulate the expression and activity of amphisomal cathepsins (79).…”

Section: Discussionmentioning

confidence: 99%

Amphisomal Route of MHC Class I Cross-Presentation in Bacteria-Infected Dendritic Cells

Fiegl

Kägebein

Liebler-Tenorio

et al. 2013

The Journal of Immunology

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Dendritic cells (DCs) are among the first professional APCs encountered by the obligate intracellular bacterium Chlamydia during infection. Using an established mouse bone marrow–derived DC line, we show that DCs control chlamydial infection in multiple small inclusions characterized by restricted bacterial growth, impaired cytosolic export of the virulence factor chlamydial protease–like activity factor, and interaction with guanylate-binding protein 1, a host cell factor involved in the initiation of autophagy. During maturation of infected DCs, chlamydial inclusions disintegrate, likely because they lack chlamydial protease–like activity factor–mediated protection. Released cytosolic Chlamydia are taken up by autophagosomes and colocalize with cathepsin-positive amphisomal vacuoles, to which peptide transporter TAP and upregulated MHC class I (MHC I) are recruited. Chlamydial Ags are subsequently generated through routes involving preprocessing in amphisomes via cathepsins and entry into the cytosol for further processing by the proteasome. Finally, bacterial peptides are reimported into the endosomal pathway for loading onto recycling MHC I. Thus, we unravel a novel pathway of MHC I–mediated cross-presentation that is initiated with a host cellular attack physically disrupting the parasitophorous vacuole, involves autophagy to collect cytosolic organisms into autophagosomes, and concludes with complex multistep antigenic processing in separate cellular compartments.

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Cathepsin S Deficiency Results in Abnormal Accumulation of Autophagosomes in Macrophages and Enhances Ang II–Induced Cardiac Inflammation

Cited by 77 publications

References 49 publications

Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration

Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration

Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy

Amphisomal Route of MHC Class I Cross-Presentation in Bacteria-Infected Dendritic Cells

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