Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

Furugen, Makoto; Higa, Futoshi; Hibiya, Kenji; Teruya, Hiromitsu; Akamine, Morikazu; Haranaga, Shusaku; Yara, Satomi; Koide, Michio; Tateyama, Masao; Mori, Nozomu; Fujita, Jiro

doi:10.1186/1465-9921-9-39

Cited by 26 publications

(20 citation statements)

References 46 publications

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“…It was reported that TGF-␤ 1 -induced A549 cells to undergo EMT (12). Legionella pneumophila, which has flagella, was reportedly able to replicate within A549 cells (6).…”

mentioning

confidence: 99%

Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells

Kondo

Higa‐Nakamine

Noguchi

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and activates host inflammatory responses, mainly through activation of the NF-κB pathway. Although pulmonary fibrosis occurs in some cases of lung infection by flagellated bacteria, the pathological roles of TLR5 stimulation in pulmonary fibrosis have yet to be elucidated. In the present study, we first confirmed that flagellin activated the NF-κB pathway in cultured A549 alveolar epithelial cells. Next, we examined the types of genes whose expression was modulated by flagellin in the cells. Microarray analysis of gene expression indicated that flagellin induced a change in gene expression that had a similar trend to transforming growth factor-β1 (TGF-β(1)), a key factor in the induction of epithelial-mesenchymal transition (EMT). Biochemical analysis revealed that TGF-β(1) and flagellin increased the level of fibronectin protein, while they reduced the level of E-cadherin protein after 30 h of treatment. Interestingly, simultaneous treatment with TGF-β(1) and flagellin significantly augmented these EMT-related changes. Flagellin strongly activated p38 MAP kinase, and the activation was sustained for longer than 30 h. SB203580, an inhibitor of p38 MAP kinase, inhibited the upregulation of fibronectin by both flagellin and TGF-β(1). Simultaneous treatment with TGF-β(1) and flagellin augmented the activation of p38 MAP kinase by TGF-β(1) or flagellin alone. These results strongly suggest that flagellin cooperates with TGF-β(1) in the induction of EMT in alveolar epithelial cells.

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“…It was reported that TGF-␤ 1 -induced A549 cells to undergo EMT (12). Legionella pneumophila, which has flagella, was reportedly able to replicate within A549 cells (6).…”

mentioning

confidence: 99%

Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells

Kondo

Higa‐Nakamine

Noguchi

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…ARDS is characterized by flooded alveolar air spaces and increased microvascular and epithelial permeability due to neutrophil inflammation, damage to the alveolar capillary endothelium, and disruption of the alveolar epithelium. Apoptotic epithelial cells are found in the damaged alveolar epithelium of patients with ARDS, implicating such a mechanism in the pathogenesis of ALI and ARDS, including immune recovery and tissue repair after injury [27]. Apoptosis was also induced in L. pneumophila-infected alveolar epithelial cells, so L. pneumophila is considered to play a key role in cytotoxicity, and some alveolar epithelial cell injury induced by L. pneumophila was attributable to apoptosis of alveolar epithelial cells [27].…”

Section: Discussionmentioning

confidence: 98%

Organizing pneumonia pattern in the follow-up CT of Legionella-infected patients

Haroon

Higa

Hibiya

et al. 2011

Journal of Infection and Chemotherapy

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“…Both, in macrophages and alveolar epithelial cells the virulent strain of L. pneumophila induces programmed cell death, DNA fragmentation and activation of various caspases (32,33).…”

Section: Discussionmentioning

confidence: 99%

Acute respiratory distress syndrome in patients with Legionella pneumonia

Kojičić

Gajic

2011

AMA

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Objective. The relationship between specific causative organisms and development of ARDS in pneumonia patients has not been explored. Several case reports have described the development of ARDS in patients with Legionella pneumonia. The aim is of this study was to determine frequency and outcomes of ARDS in patients with Legionella Pneumonia. Methods. A retrospective cohort study of patients with Legionella pneumonia hospitalized at two Mayo Clinic Rochester hospitals was conducted. To identify the patients with Legionella pneumonia we searched the Mayo Clinic Life Sciences System (MCLSS) database from 01/01/2003 to 12/31/2007. Electronic medical records of patients with active Legionella pneumonia based on positive cultures and/or urinary antigen were reviewed. ARDS was diagnosed on the basis of the criteria of the North American/European consensus conference definition. Results. We identified 15 patients with microbiologically proven Legionella pneumonia of whom 11 were admitted to the intensive care unit (ICU), 6 required mechanical ventilation and 5 met the criteria for ARDS. Age (median 42 vs. 50 years, p=0.32) and gender (4/10 vs. 1/5 female, p=0.60) were similar in patients with and without ARDS. Septic shock was present in 4 of the 5 patients with ARDS and only 1 without. Patients with ARDS had longer ICU length of stay (median 9 vs. 1 days, P=0.03). Only one patient (from the ARDS group) died in the hospital. Conclusion. In this retrospective study ARDS occurred in one third of patients with microbiologically proven Legionella pneumonia and was associated with prolonged length of ICU stay.

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Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

Cited by 26 publications

References 46 publications

Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells

Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells

Organizing pneumonia pattern in the follow-up CT of Legionella-infected patients

Acute respiratory distress syndrome in patients with Legionella pneumonia

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