<i>Actinobacillus actinomycetemcomitans</i> induces lethal effects on the macrophage‐like human cell line U937

Fukunaga, M; Tsuruda, Keiko

doi:10.1034/j.1399-302x.2001.016005284.x

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…tions consistent with apoptosis (Korostoff et al, 1998;Fukunaga & Tsuruda, 2001). Therefore, three strains of A. actinomycetemcomitans, Y4, 652 and leukotoxin geneinserted 652 (652 tltx ), were employed in this investigation.…”

Section: Discussionmentioning

confidence: 99%

Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells

Kato

Sugimura

Nakashima

et al. 2005

Journal of Medical Microbiology

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It has previously been reported that the murine macrophage cell line J774.1 and the human oral epithelial cell line KB undergo apoptosis as a result of Actinobacillus actinomycetemcomitans infection. Recent studies have demonstrated that apoptosis regulation is modulated by multiple phosphorylation of several different protein kinases, including the major subtypes of the mitogen-activated protein kinase (MAPK) family. The MAPK family promotes cell survival and/or proliferation in response to growth factor stimulation, or apoptosis in response to various stress stimuli. The primary objective of the present investigation was to clarify whether human immune cells undergo apoptosis following A. actinomycetemcomitans infection and, if so, to establish the involvement of the MAPK family. Human monocytic THP-1 cells were infected with A. actinomycetemcomitans in microtubes. Lactate dehydrogenase release into the culture supernatant and DNA fragmentation in the cells were monitored. DNA fragmentation was also identified by agarose gel electrophoresis. Cell death following A. actinomycetemcomitans infection occurred by apoptosis, shown by an increase in the proportion of fragmented DNA and the typical ladder pattern of DNA fragmentation indicative of apoptosis. Furthermore, p38 MAPK activity and tumour necrosis factor alpha (TNF-α) levels increased following A. actinomycetemcomitans infection. In contrast, cell death and TNF-α levels in infected cells decreased upon addition of a p38 inhibitor or an anti-TNF-α antibody. However, exogenous TNF-α could not induce apoptosis in uninfected THP-1 cells. Interestingly, p38 MAPK activity diminished in the presence of anti-TNF-α antibody. These findings indicated that A. actinomycetemcomitans infection induces apoptosis in THP-1 cells and that p38 MAPK activity is directly involved in apoptosis. TNF-α may play an indirect role in apoptosis via enhanced p38 MAPK activity. A. actinomycetemcomitans-induced apoptosis of human immune cells may be important in terms of initiation and progression of periodontal diseases.

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Section: Discussionmentioning

confidence: 99%

Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells

Kato

Sugimura

Nakashima

et al. 2005

Journal of Medical Microbiology

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“…It is well recognised that alveolar macrophages and their precursors, circulating monocytes, play a key role in airway inflammatory diseases ( Arm & Lee, 1992 ; Spina et al ., 1998a ; Barnette & Underwood, 2000 ; Jeffery, 2000 ; Giembycz, 2002 ; Barnes, 2003 ) and we have set out here using the human U937 cell line to define the PDE4 isoforms expressed in both their monocytic and macrophage‐like states ( Hass et al ., 1989 ; Twomey et al ., 1993 ; Kuroda et al ., 1997 ; Fukunaga & Tsuruda, 2001 ; Matheson et al ., 2002 ). Intriguingly, it has been shown ( Tenor et al ., 1995 ; Gantner et al ., 1997 ; Bender et al ., 2004 ) that the in vitro differentiation of both peripheral blood‐derived and alveolar monocytes to macrophages leads to a marked downregulation of PDE4 activity, concomitant with an upregulation of PDE3 and PDE1 activities.…”

Section: Discussionmentioning

confidence: 99%

“…In experiments comparing differentiated, ‘macrophage‐like’ U937 cells to control, ‘monocyte‐like’ U937 cells, then cells from the same passage were used. U937 cell differentiation was achieved as described previously by others ( Hass et al ., 1989 ; Twomey et al ., 1993 ; Kuroda et al ., 1997 ; Fukunaga & Tsuruda, 2001 ; Matheson et al ., 2002 ). Briefly, this was done by incubating 1 × 10 6 cells ml −1 with complete RPMI medium supplemented with 4 n M PMA for a total of 4 days.…”

Section: Methodsmentioning

confidence: 99%

“…Analyses of blood and airway derived monocytic and macrophage cells are hampered by subject variability and availability of material as well as the small numbers of cells that can be derived, making it difficult to perform identification of low abundance signalling proteins such as PDE4 isoforms. We thus set out here to analyse a model system, namely the human U937 monocytic cell line, which has been shown to be capable of PMA‐induced differentiation to adopt a macrophage‐like phenotype ( Hass et al ., 1989 ; Twomey et al ., 1993 ; Kuroda et al ., 1997 ; Fukunaga & Tsuruda, 2001 ; Matheson et al ., 2002 ).…”

Section: Introductionmentioning

confidence: 99%

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Remodelling of the PDE4 cAMP phosphodiesterase isoform profile upon monocyte‐macrophage differentiation of human U937 cells

Shepherd

Baillie

Stirling³

et al. 2004

British J Pharmacology

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1 Monocytes and macrophages provide key targets for the action of novel anti-inflammatory therapeutics targeted at inhibition of PDE4 cAMP-specific phosphodiesterases. 2 PDE4 enzymes provide the dominant cAMP phosphodiesterase activity in U937 human monocytic cells. 3 Differentiation of U937 monocytic cells to a macrophage-like phenotype causes a marked reduction in total cellular PDE4 activity. 4 Monocytic U937 cells express the long PDE4A4, PDE4D5 and PDE4D3 isoforms plus the short PDE4B2 isoform. Differentiation of U937 cells to a macrophage-like phenotype causes a marked downregulation of PDE4D3 and PDE4D5, elicits a marked upregulation of PDE4B2 and induces the novel PDE4A10 long isoform. Comparable patterns are found in human peripheral blood monocytes and macrophages differentiated from them. 5 Immunopurification of PDE4 subfamilies identifies long PDE4D isoforms as providing the major PDE4 activity in U937 monocytic cells. 6 In U937 macrophage-like cells, the activity of the short PDE4B2 isoform predominates. 7 No indication of either the expression or induction of PDE4C was evident. 8 Activation of ERK exerts an inhibitory effect on total PDE4 activity in monocytic U937 cells, where the activity of long PDE4 isoforms predominates. 9 The effect of ERK activation is switched to one of overall stimulation of total PDE4 activity in macrophage U937 cells, where the activity of the short PDE4B2 isoform predominates. 10 The profound differentiation-induced changes in PDE4 isoform profile identified here suggests that the development of inhibitors specific for particular PDE4 isoforms may allow for selective effects on monocytes and macrophages to be achieved.

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“…Thereafter, the cells were incubated in PMA‐free supplemented RPMI 1640 medium for 24 h prior to use. Following this treatment, more than 90% of U937 cells are alive and differentiated into macrophages loosely attached to the plastic surface (4). The floating cells were then removed and adherent macrophage‐like cells were collected using a cell scraper.…”

Section: Cultivation and Differentiation Of U937 Cellsmentioning

confidence: 99%

Binding of Actinobacillus actinomycetemcomitans lipopolysaccharides to Peptostreptococcus micros stimulates tumor necrosis factor α production by macrophage‐like cells

Yoshioka

Grenier

Mayrand

2005

Oral Microbiology and Immunology

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Peptostreptococcus micros is a gram-positive bacterium that has been associated with periodontitis and endodontic infections. In this study, we hypothesized that P. micros binds the immunomodulating component lipopolysaccharide derived from gram-negative bacteria to increase its capacity to stimulate cytokine production by host cells. The ability of P. micros to bind Actinobacillus actinomycetemcomitans lipopolysaccharide was demonstrated by an enzyme-linked immunosorbent assay and by immunoelectron microscopy. Pretreatment of P. micros cells with A. actinomycetemcomitans lipopolysaccharide was associated with a 49-fold increase in tumor necrosis factor alpha production by human monocytic cells U937 differentiated into adherent macrophages, compared to the stimulation with untreated P. micros. This effect was suppressed by incorporating polymyxin B, a lipid A-binding substance, during treatment of macrophage-like cells with lipopolysaccharide-coated P. micros cells. This is the first study reporting a binding interaction between lipopolysaccharide and a gram-positive bacterium. This interaction represents a new mechanism that could promote the inflammatory response during periodontitis.

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Actinobacillus actinomycetemcomitans induces lethal effects on the macrophage‐like human cell line U937

Cited by 8 publications

References 31 publications

Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells

Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells

Remodelling of the PDE4 cAMP phosphodiesterase isoform profile upon monocyte‐macrophage differentiation of human U937 cells

Binding of Actinobacillus actinomycetemcomitans lipopolysaccharides to Peptostreptococcus micros stimulates tumor necrosis factor α production by macrophage‐like cells

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