<i>Streptococcus pneumoniae</i>-induced regulation of cyclooxygenase-2 in human lung tissue

Szymanski, Kolja; Toennies, Mario; Becher, Anne; Fatykhova, Diana; N′Guessan, Philippe Dje; Gutbier, Birgitt; Klauschen, Frederick; Neuschaefer-Rube, Frank; Schneider, Paul; Rueckert, Jens C.; Neudecker, Jens; Bauer, Torsten T.; Dalhoff, K; Drömann, Daniel; Gruber, Achim D.; Kershaw, Olivia; Temmesfeld-Wollbrueck, Bettina; Suttorp, Norbert; Hippenstiel, Stefan; Hocke, Andreas C.

doi:10.1183/09031936.00186911

Cited by 52 publications

(57 citation statements)

References 39 publications

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“…The prominent role of pneumococcal DNA and TLR9 for KLF4 induction is shown by experiments using purified pneumococcal DNA, CpG DNA, siRNA based silencing of TLR9 and TLR9 inhibiting oligonucleotides as well as LytA-deficient pneumococci unable to liberate DNA (6). The activity of LytA degrades the pneumococcal cell wall, resulting in the lysis of the bacteria and thereby the liberation of pneumococcal cell wall components that are able to activate, e.g., TLR2.…”

Section: Discussionmentioning

confidence: 98%

Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium

Zahlten

Herta

Kabus

et al. 2015

Am J Respir Cell Mol Biol

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In severe pneumococcal pneumonia, the delicate balance between a robust inflammatory response necessary to kill bacteria and the loss of organ function determines the outcome of disease. In this study, we tested the hypothesis that Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneumoniae-related human lung epithelial cell activation using the potent proinflammatory chemokine IL-8 as a model molecule. Pneumococci induced KLF4 expression in human lung, in primary human bronchial epithelial cells, and in the lung epithelial cell line BEAS-2B. Whereas proinflammatory cell activation depends mainly on the classical Toll-like receptor 2-mitogen-activated protein kinase or phosphatidylinositide 3-kinase and NF-κB pathways, the induction of KLF4 occurred independently of these molecules but relied, in general, on tyrosine kinase activation and, in part, on the src kinase family member yamaguchi sarcoma viral oncogene homolog (yes) 1. The up-regulation of KLF4 depended on the activity of the main pneumococcal autolysin LytA. KLF4 overexpression suppressed S. pneumoniae-induced NF-κB and IL-8 reporter gene activation and release, whereas small interfering RNA-mediated silencing of KLF4 or yes1 kinase led to an increase in IL-8 release. The KLF4-dependent down-regulation of NF-κB luciferase activity could be rescued by the overexpression of the histone acetylase p300/cAMP response element-binding protein-associated factor. In conclusion, KLF4 acts as a counter-regulatory transcription factor in pneumococci-related proinflammatory activation of lung epithelial cells, thereby potentially preventing lung hyperinflammation and subsequent organ failure.

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Section: Discussionmentioning

confidence: 98%

Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium

Zahlten

Herta

Kabus

et al. 2015

Am J Respir Cell Mol Biol

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“…While these studies advance our understanding of neutrophil recruitment and killing, experimental depletion of neutrophils in murine pneumococcal pneumonia models has previously revealed serotype-specific effects ranging from deleterious to a beneficial effect on lethality [81–83]. In another recent study, pro-inflammatory responses to pneumococcus were modulated by MAPK-dependent induction of COX-2 in response to pneumococcal pneumonia, leading to prostaglandin release [84], revealing a novel mechanism by which the inflammatory consequences of neutrophil killing are modulated.…”

Section: The Role Of Host Inflammation In Pneumococcal Pneumoniamentioning

confidence: 99%

Current concepts in host–microbe interaction leading to pneumococcal pneumonia

Vernatter

Pirofski

2013

Current Opinion in Infectious Diseases

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Purpose of review Infection with Streptococcus pneumoniae (pneumococcus) results in colonization, which can lead to local or invasive disease, of which pneumonia is the most common manifestation. Despite the availability of pneumococcal vaccines, pneumococcal pneumonia is the leading cause of community and in-hospital pneumonia in the United States and globally. This article discusses new insights into the pathogenesis of pneumococcal disease. Recent findings The host-microbe interactions that determine whether pneumococcal colonization will result in clearance or invasive disease are highly complex. This paper focuses on new information in three areas that bear on the pathogenesis of pneumococcal disease: 1) factors that govern colonization, the prelude to invasive disease, including effects on colonization and invasion of capsular serotype, pneumolysin, surface proteins that regulate complement deposition, biofilm formation and agglutination; 2) the effect of co-infection with other bacteria and viruses on pneumococcal growth and virulence, including the synergistic effect of influenza; and 3) the contribution of the host inflammatory response to the pathogenesis of pneumococcal pneumonia, including the effects of pattern recognition molecules, cells that enhance and modulate inflammation, and therapies that modulate inflammation, such as statins. Summary Recent research on pneumococcal pathogenesis reveals new mechanisms by which microbial factors govern the ability of pneumococcus to progress from the state of colonization to disease and host inflammatory responses contribute to the development of pneumonia. These mechanisms suggest that therapies which modulate the inflammatory response could hold promise for ameliorating damage due to the inflammatory response in pneumococcal disease.

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“…The earlier presence of surfactant in female neonatal lungs helps open the small airways and may contribute to their higher airflow rate observed [50]. Evidence from human studies suggests that male infants are more susceptible to lung infection, with greater associated morbidity and mortality than female infants, but the reverse is applied in children and adolescents [47,51,52]. Regarding respiratory tract infections (RTIs), women are more 3.…”

Section: Gender Differences In Community-acquired Pneumoniamentioning

confidence: 99%

“…that is also highly expressed in mouse and human lungs after infection is prostaglandin E (PGE 2 ), and its precursor enzyme cyclooxygenase-2 (COX2) [52]. Studies using depletion of alveolar macrophages have demonstrated that these contribute largely to the stimulation of pro-inflammatory cytokines, such as IL-6 and TNFα [48].…”

Section: Strain Differences and Associated Mechanismsmentioning

confidence: 99%

Understanding the Intersection of Environmental Pollution, Pneumonia, and Inflammation: Does Gender Play a Role?

Silveyra¹,

Fuentes²,

Rivera³

2017

Contemporary Topics of Pneumonia

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Accumulating evidence indicates that exposure to air pollution is associated with increased mortality from respiratory disease. Exposure to ambient pollutants, such as ozone, particulate matter, sulfur dioxide, nitrogen dioxide, and other agents has been associated with decrease in lung function and immunity, and with increased rates of hospitalization for lung disease, including pneumonia. Furthermore, sex differences in frequency and severity of pulmonary disease and infection have been reported, suggesting a role of sex hormones in mediating these differences. Pneumonia, which is commonly caused by bacterial infection and subsequent lung inflammation leading to hospitalization and death, occurs at different rates in men and women. In this context, male and female hormones can have direct effects on the immunity system by binding to receptors in immune cells, and these responses can be modulated by environmental exposures. This chapter summarizes clinical, animal, and epidemiological studies linking exposure to air pollution and pneumonia in both males and females. Understanding sex-specific mechanisms in pneumonia pathogenesis and environmental responses can help in the development of more effective therapeutics and treatment options to reduce negative health outcomes in men and women.

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Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue

Cited by 52 publications

References 39 publications

Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium

Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium

Current concepts in host–microbe interaction leading to pneumococcal pneumonia

Understanding the Intersection of Environmental Pollution, Pneumonia, and Inflammation: Does Gender Play a Role?

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