Azithromycin reduces the viability of human bronchial smooth muscle cells

Stamatiou, Rodopi; Boukas, Konstantinos; Paraskeva, Efrosyni; Molyvdas, Paschalis-Adam; Hatziefthimiou, Apostolia

doi:10.1038/ja.2009.125

Cited by 16 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fourth, flow cytometry analysis showed that moderate concentrations of TNF- α promoted PDLSC apoptosis and that AZM mitigated this process. Our finding that AZM can inhibit the apoptosis of PDLSCs is consistent with the work of Mizunoe et al [ 42 ] and Stamatiou et al [ 43 ].…”

Section: Discussionsupporting

confidence: 93%

Azithromycin Promotes the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells after Stimulation with TNF-α

Meng

Zhou

et al. 2018

Stem Cells International

View full text Add to dashboard Cite

Background and Objective This study investigated the effects and underlying mechanisms of azithromycin (AZM) treatment on the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) after their stimulation with TNF-α in vitro. Methods. PDLSCs were isolated from periodontal ligaments from extracted teeth, and MTS assay was used to evaluate whether AZM and TNF-α had toxic effects on PDLSCs viability and proliferation. After stimulating PDLSCs with TNF-α and AZM, we analyzed alkaline phosphatase staining, alkaline phosphatase activity, and alizarin red staining to detect osteogenic differentiation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the mRNA expression of osteogenic-related genes, including RUNX2, OCN, and BSP. Western blotting was used to measure the NF-κB signaling pathway proteins p65, phosphorylated p65, IκB-α, phosphorylated IκB-α, and β-catenin as well as the apoptosis-related proteins caspase-8 and caspase-3. Annexin V assay was used to detect PDLSCs apoptosis. Results TNF-α stimulation of PDLSCs decreased alkaline phosphatase and alizarin red staining, alkaline phosphatase activity, and mRNA expression of RUNX2, OCN, and BSP in osteogenic-conditioned medium. AZM enhanced the osteogenic differentiation of PDLSCs that were stimulated with TNF-α. Western blot analysis showed that β-catenin, phosphorated p65, and phosphorylated IκB-α protein expression decreased in PDLSCs treated with AZM. In addition, pretreatment of PDLSCs with AZM (10 μg/ml, 20 μg/ml) prevented TNF-α-induced apoptosis by decreasing caspase-8 and caspase-3 expression. Conclusions Our results showed that AZM promotes PDLSCs osteogenic differentiation in an inflammatory microenvironment by inhibiting the WNT and NF-κB signaling pathways and by suppressing TNF-α-induced apoptosis. This suggests that AZM has potential as a clinical therapeutic for periodontitis.

show abstract

Section: Discussionsupporting

confidence: 93%

Azithromycin Promotes the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells after Stimulation with TNF-α

Meng

Zhou

et al. 2018

Stem Cells International

View full text Add to dashboard Cite

show abstract

“…Among these, the PI3-kinase acts as a major upstream mTOR activator. Previous studies have implied that treatment with AZM leads to activation of PI3-K 51 52 . However, using an in vitro kinase assay, we could not observe a direct effect of AZM on PI3-K activity.…”

Section: Discussionmentioning

confidence: 98%

Azithromycin suppresses CD4+ T-cell activation by direct modulation of mTOR activity

Ratzinger

Haslacher

Poeppl

et al. 2014

Sci Rep

View full text Add to dashboard Cite

Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4+ T-cells. Isolated CD4+ T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4+ T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4+ T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides.

show abstract

“…The potential apoptotic effect of AZM has been examined in neutrophils, peripheral blood mononuclear cells and tracheal smooth muscle cells [8,10,11]. In agreement with these findings, AZM displayed the ability to induce apoptosis of Hela, SGC-7901 and BHK-21 cells at a comparable degree in vitro , as determined by an annexin V-FITC binding assay (Figure 3B), although it showed a preferential anti-proliferative activity to cancer over transformed cells (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…This unique metabolic feature leads AZM to possess the favorable property of rapidly accumulating and slowly releasing into cells and tissues, resulting in a higher local concentration of drug, and a longer elimination half-life [7]. Like other macrolides, apart from its antimicrobial properties, AZM also exhibits anti-inflammation, immunomodulation, and anti-proliferation effects, as well as an autophagic effect by leading to apoptotic cell death [8,9]. AZM has shown an ability to induce neutrophil apoptosis, as well as inhibit proliferation of peripheral blood mononuclear cells [10]; these have been suggested to contribute the anti-inflammatory activity induced by AZM [11,12,13].…”

Section: Introductionmentioning

confidence: 99%

“…AZM has shown an ability to induce neutrophil apoptosis, as well as inhibit proliferation of peripheral blood mononuclear cells [10]; these have been suggested to contribute the anti-inflammatory activity induced by AZM [11,12,13]. Additionally, AZM has shown an ability to suppress the proliferation of tracheal smooth muscle cells (SMCs) through a mechanism of induction of apoptotic cell death [8], and reverse resistance of P-glycoprotein-dependent anticancer drugs in vitro [14]. However, the effect of AZM on cancer cell apoptosis and its interactions with commonly used anti-cancer agents have not been investigated yet.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

Zhou

Zhang

et al. 2012

Cancers

View full text Add to dashboard Cite

In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC50) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs.

show abstract

Azithromycin reduces the viability of human bronchial smooth muscle cells

Cited by 16 publications

References 31 publications

Azithromycin Promotes the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells after Stimulation with TNF-α

Azithromycin Promotes the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells after Stimulation with TNF-α

Azithromycin suppresses CD4+ T-cell activation by direct modulation of mTOR activity

Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

Contact Info

Product

Resources

About