CCAAT/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage-mediated phagocytosis of dying neuron cells

Ko, Chiung-Yuan; Chang, Ling-Hua; Lee, Yi Chao; Sterneck, Esta; Cheng, Chun-Pei; Chen, Shun Hua; Huang, A-Mei; Tseng, Joseph T.; Wang, Ju‐Ming

doi:10.1016/j.neurobiolaging.2010.09.017

Cited by 64 publications

(96 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also noted that expression of TSG-6, 18 PTX3, MMP-1, and MMP-3 transcripts was all upregulated by TNF-a and IL-1b in a manner similar to overexpression of CCAAT/enhancer binding protein delta (CEBPD) in U373MG cells. 40 To resolve their interrelationship, we used PTX3 knockdown to demonstrate further upregulation transcription and activation of MMP-1 and MMP-3 in normal and CCh fibroblasts (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

Guo

Zhang

et al. 2012

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. Conjunctivochalasis (CCh) is an age-related inflammatory ocular surface disease manifesting redundant, loose conjunctiva folds. The pathogenic role of Pentraxin 3 (PTX3) in controlling upregulation of matrix metalloproteinase 1 (MMP-1) and MMP-3 in CCh remains undefined.METHODS. Cytolocation of PTX3 and apoptosis were compared by immunostaining and terminal deoxyribonucleotidyl transferase-mediated FITC-linked dUTP nick-end DNA labeling (TUNEL) assay between normal and CCh specimens containing the conjunctiva and the Tenon. Second to third cultures of normal and CCh fibroblasts were treated with or without Aprotinin, Batimastat, or N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), followed by transfection with or without PTX3 siRNA, and TNF-a or IL-1b. Cell lysates and culture media were collected to assess apoptosis measured by the Cell Death Detection ELISA and expression of PTX3, MMP-1, and MMP-3 transcripts and proteins by quantitative RT-PCR and Western blot, respectively. RESULTS. PTX3 immunostaining was negative in normal specimens, but strongly positive in the subconjunctival stroma of CCh specimens. More apoptotic cells were found in CCh samples than in normal specimens. Expression of PTX3 transcripts and protein was not constitutive in resting normal fibroblasts but was in resting CCh fibroblasts and was upregulated by IL-1b in both cell lysates and culture media of both fibroblasts. PTX3 siRNA further upregulated MMP-1 and MMP-3 transcripts in resting normal fibroblasts, but synergistically with IL-1b upregulated the expression of MMP-1 and MMP-3 transcripts only in CCh fibroblasts, with activation of MMP-1 more so than MMP-3. PTX3 siRNA knockdown also promoted cell death characterized by apoptosis and necrosis, and such cell death could be rescued by inhibitors against serine proteinase, MMP1, or MMP3.CONCLUSIONS. Perturbation of PTX3 expression might partake in apoptosis and pathogenesis of CCh by upregulating expression of MMP-1 and MMP-3, and activation of MMP-1 and MMP-3.

show abstract

Section: Discussionmentioning

confidence: 99%

PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

Guo

Zhang

et al. 2012

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…The microglia-mediated Aβ clearance by phagocytosis has been mentioned (Simard et al, 2006;Lee and Landreth, 2010) but the phagocytotic activity is reduced in AD patients (Fiala et al, 2005;Fiala et al, 2007). The activation of astrocytic CEBPD was thought to attenuate the macrophage-mediated phagocytosis of damaged neurons and regulate the migration and activation of microglia and macrophages (Ko et al, 2012;Ko et al, 2014).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The CCAAT/enhancer-binding protein delta/miR135a/thrombospondin 1 axis mediates PGE2-induced angiogenesis in Alzheimer's disease

Chu

Narumiya³

et al. 2015

Neurobiology of Aging

Self Cite

View full text Add to dashboard Cite

“…Several studies have suggested that the p38/CREB (cAMP responsive element binding protein) and JAK/ STAT3 pathways play crucial roles in CEBPD transcriptional activation (10,11). Previous studies have also suggested that CEBPD plays a vital role in inflammation and inflammatory disease processes (12,13). However, unlike the inflammatory effectors NF-kB and STAT3 that are consistently activated in cancer cells, CEBPD inactivation has been observed in several types of cancer, including cervical and hepatocellular carcinoma (10,14), breast (15), prostate cancer (9), and leukemia (16).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

Wang

Chu

et al. 2017

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Cisplatin (CDDP) is frequently used in combination chemotherapy with paclitaxel for treating urothelial carcinoma of the urinary bladder (UCUB). CDDP cross-resistance has been suggested to develop with paclitaxel, thus hindering successful UCUB treatment. Therefore, elucidating the mechanisms underlying CDDP-induced anticancer drug resistance is imperative and may provide an insight in developing novel therapeutic strategy.Experimental Design: Loss-of-function assays were performed to elucidate the role of the EGFR and STAT3 in CDDP-induced CCAAT/enhancer-binding protein delta (CEBPD) expression in UCUB cells. Reporter and in vivo DNA-binding assays were employed to determine whether CEBPD directly regulates ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily C member 2 (ABCC2) activation. Finally, a xenograft animal assay was used to examine the abilities of gefitinib and S3I-201 (a STAT3 inhibitor) to reverse CDDP and paclitaxel sensitivity.Results: CEBPD expression was maintained in postoperative chemotherapy patients, and this expression was induced by CDDP even in CDDP-resistant UCUB cells. Upon CDDP treatment, CEBPD activated ABCB1 and ABCC2. Furthermore, the EGFR/STAT3 pathway contributed to CDDP-induced CEBPD expression in UCUB cells. Gefitinib and S3I-201 treatment significantly reduced the expression of CEBPD and enhanced the sensitivity of CDDP-resistant UCUB cells to CDDP and paclitaxel.Conclusions: Our results revealed the risk of CEBPD activation in CDDP-resistant UCUB cells and suggested a therapeutic strategy for patients with UCUB or UCUB resisted to CDDP and paclitaxel by combination with either gefitinib or S3I-201.

show abstract

CCAAT/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage-mediated phagocytosis of dying neuron cells

Cited by 64 publications

References 63 publications

PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

The CCAAT/enhancer-binding protein delta/miR135a/thrombospondin 1 axis mediates PGE2-induced angiogenesis in Alzheimer's disease

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

Contact Info

Product

Resources

About