scholarly journals Exposure to Porphyromonas gingivalis Induces Production of Proinflammatory Cytokine via TLR2 from Human Respiratory Epithelial Cells

2020 ◽  
Vol 9 (11) ◽  
pp. 3433 ◽  
Author(s):  
Norihisa Watanabe ◽  
Sho Yokoe ◽  
Yorimasa Ogata ◽  
Shuichi Sato ◽  
Kenichi Imai
Keyword(s):  
Epithelial Cells ◽  
Porphyromonas Gingivalis ◽  
Aspiration Pneumonia ◽  
Chronic Periodontitis ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Proinflammatory Cytokine Production ◽  
Respiratory Epithelial Cells ◽  
Periodontopathic Bacteria ◽  
Respiratory Epithelial

Aspiration pneumonia is a major health problem owing to its high mortality rate in elderly people. The secretion of proinflammatory cytokines such as interleukin (IL)-8 and IL-6 by respiratory epithelial cells, which is induced by infection of respiratory bacteria such as Streptococcus pneumoniae, contributes to the onset of pneumonia. These cytokines thus play a key role in orchestrating inflammatory responses in the lower respiratory tract. In contrast, chronic periodontitis, a chronic inflammatory disease caused by the infection of periodontopathic bacteria, typically Porphyromonas gingivalis, is one of the most prevalent microbial diseases affecting humans globally. Although emerging evidence has revealed an association between aspiration pneumonia and chronic periodontitis, a causal relationship between periodontopathic bacteria and the onset of aspiration pneumonia has not been established. Most periodontopathic bacteria are anaerobic and are therefore unlikely to survive in the lower respiratory organs of humans. Therefore, in this study, we examined whether simple contact by heat-inactivated P. gingivalis induced proinflammatory cytokine production by several human respiratory epithelial cell lines. We found that P. gingivalis induced strong IL-8 and IL-6 secretion by BEAS-2B bronchial epithelial cells. P. gingivalis also induced strong IL-8 secretion by Detroit 562 pharyngeal epithelial cells but not by A549 alveolar epithelial cells. Additionally, Toll-like receptor (TLR) 2 but not TLR4 was involved in the P. gingivalis-induced proinflammatory cytokine production. Furthermore, P. gingivalis induced considerably higher IL-8 and IL-6 production than heat-inactivated S. pneumoniae. Our results suggest that P. gingivalis is a powerful inflammatory stimulant for human bronchial and pharyngeal epithelial cells and can stimulate TLR2-mediated cytokine production, thereby potentially contributing to the onset of aspiration pneumonia.

scholarly journals Candida albicans Cell Wall Glycosylation May Be Indirectly Required for Activation of Epithelial Cell Proinflammatory Responses

2011 ◽  
Vol 79 (12) ◽  
pp. 4902-4911 ◽  
Author(s):  
Celia Murciano ◽  
David L. Moyes ◽  
Manohursingh Runglall ◽  
Ayesha Islam ◽  
Celine Mille ◽  
...  
Keyword(s):  
Cell Wall ◽  
Epithelial Cells ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Cell Damage ◽  
Proinflammatory Cytokine Production ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Hypha Formation ◽  
Oral Epithelial

ABSTRACTOral epithelial cells discriminate between the yeast and hyphal forms ofCandida albicansvia the mitogen-activated protein kinase (MAPK) signaling pathway. This occurs through phosphorylation of the MAPK phosphatase MKP1 and activation of the c-Fos transcription factor by the hyphal form. Given that fungal cell wall polysaccharides are critical in host recognition and immune activation in myeloid cells, we sought to determine whether β-glucan andN- orO-glycosylation was important in activating the MAPK/MKP1/c-Fos hypha-mediated response mechanism and proinflammatory cytokines in oral epithelial cells. Using a series of β-glucan andN- andO-mannan mutants, we found thatN-mannosylation (via Δoch1and Δpmr1mutants) andO-mannosylation (via Δpmt1and Δmnt1Δmnt2mutants), but not phosphomannan (via a Δmnn4mutant) or β-1,2 mannosylation (via Δbmt1to Δbmt6mutants), were required for MKP1/c-Fos activation, proinflammatory cytokine production, and cell damage induction. However, theN- andO-mannan mutants showed reduced adhesion or lack of initial hypha formation at 2 h, resulting in little MKP1/c-Fos activation, or restricted hypha formation/pseudohyphal formation at 24 h, resulting in minimal proinflammatory cytokine production and cell damage. Further, the α-1,6-mannose backbone of theN-linked outer chain (corresponding to a Δmnn9mutant) may be required for epithelial adhesion, while the α-1,2-mannose component of phospholipomannan (corresponding to a Δmit1mutant) may contribute to epithelial cell damage. β-Glucan appeared to play no role in adhesion, epithelial activation, or cell damage. In summary,N- andO-mannosylation defects affect the ability ofC. albicansto induce proinflammatory cytokines and damage in oral epithelial cells, but this may be due to indirect effects on fungal pathogenicity rather than mannose residues being direct activators of the MAPK/MKP1/c-Fos hypha-mediated immune response.

scholarly journals Bacterial Siderophores That Evade or Overwhelm Lipocalin 2 Induce Hypoxia Inducible Factor 1α and Proinflammatory Cytokine Secretion in Cultured Respiratory Epithelial Cells

2014 ◽  
Vol 82 (9) ◽  
pp. 3826-3836 ◽  
Author(s):  
Victoria I. Holden ◽  
Steven Lenio ◽  
Rork Kuick ◽  
Sadeesh K. Ramakrishnan ◽  
Yatrik M. Shah ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Proinflammatory Cytokine ◽  
Hypoxia Inducible Factor ◽  
Iron Chelation ◽  
Protein Stabilization ◽  
Host Protein ◽  
Lipocalin 2 ◽  
Respiratory Epithelial Cells ◽  
Hypoxia Inducible Factor 1Α ◽  
Respiratory Epithelial

ABSTRACTIron is essential for many cellular processes and is required by bacteria for replication. To acquire iron from the host, pathogenic Gram-negative bacteria secrete siderophores, including enterobactin (Ent). However, Ent is bound by the host protein lipocalin 2 (Lcn2), preventing bacterial reuptake of aferric or ferric Ent. Furthermore, the combination of Ent and Lcn2 (Ent+Lcn2) leads to enhanced secretion of interleukin-8 (IL-8) compared to that induced by either stimulus alone. Modified or structurally distinct siderophores, including yersiniabactin (Ybt) and glycosylated Ent (GlyEnt, or salmochelin), deliver iron to bacteria despite the presence of Lcn2. We hypothesized that the robust immune response to Ent and Lcn2 requires iron chelation rather than the Ent+Lcn2 complex itself and also can be stimulated by Lcn2-evasive siderophores. To test this hypothesis, cultured respiratory epithelial cells were stimulated with combinations of purified siderophores and Lcn2 and analyzed by gene expression microarrays, quantitative PCR, and cytokine immunoassays. Ent caused HIF-1α protein stabilization, induced the expression of genes regulated by hypoxia-inducible factor 1α (HIF-1α), and repressed genes involved in cell cycle and DNA replication, whereas Lcn2 induced expression of proinflammatory cytokines. Iron chelation by excess Ent or Ybt significantly increased Lcn2-induced secretion of IL-8, IL-6, and CCL20. Stabilization of HIF-1α was sufficient to enhance Lcn2-induced IL-6 secretion. These data indicate that respiratory epithelial cells can respond to bacterial siderophores that evade or overwhelm Lcn2 binding by increasing proinflammatory cytokine production.

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