Growth and adherence of Staphylococcus aureus were enhanced through the PGE2 produced by the activated COX-2/PGE2 pathway of infected oral epithelial cells

Abstract

Staphylococcus aureus is a major pathogen of varieties of oral mucous infection. Prostaglandin E2 (PGE2) is a pro-inflammatory factor and Cyclooxygenase 2 (COX-2) is a critical enzyme of PGE2 biosynthesis. The purpose of this study is to investigate whether Staphylococcus aureus can increase PGE2 production of oral epithelial cells and how PGE2 functions in the growth and adherence of Staphylococcus aureus. mRNA levels of COX-2, fnbpA and fnbpB were estimated by quantitative PCR. PGE2 production was measured by Enzyme Linked Immunosorbent Assay (ELISA). The binding biomass of Staphylococcus aureus to human fibronectin was investigated by crystal violet staining and confocal laser scanning microscopy and the adherent force was measured by atomic force microscope (AFM). The COX-2 mRNA level and PGE2 production were increased by Staphylococcus aureus. PGE2 promoted the growth and biofilm formation of Staphylococcus aureus, enhanced the attachment of Staphylococcus aureus to the human fibronectin as well as to the HOK cells. The transcription of fnbpB was up-regulated by PGE2 in both early and middle exponential phase but not fnbpA. These results suggest that the activation of COX-2/PGE2 pathway in oral epithelial cell by Staphylococcus aureus can in turn facilitate the growth and the ability to adhere of the pathogen. These findings uncover a new function of PGE2 and may lead to the potential of COX-2/PGE2 targeting in the therapy of inflammation and cancer in both which the COX-2/PGE2 pathway were observed activated.

Staphylococcus aureus induces COX-2-dependent proliferation and malignant transformation in oral keratinocytes

“…The induction of COX-2 by S. aureus in HOK cells was found in our previous study [19], but that study did not fully reveal the functional mediator(s) exerting the inductive effect. Thus, using heat-inactivated S. aureus and supernatants from S. aureus cultures, we investigated whether the live cells or the secretory components of S. aureus were essential for the activation of the COX-2/PGE 2 pathway in HOK cells.…”

“…In our previous study, we found that S. aureus can induce Cyclooxygenase-2 (COX-2) expression and PGE 2 production in human oral keratinocyte (HOK) cells [19]. COX-2 is an enzyme that mediates the synthesis of prostaglandins (PGE 2 , PGD 2 , PGF2α, PGI 2 , and thromboxane) and plays an important role in the inflammatory response [20].…”

AgCuB nanoparticle eradicates intracellular S. aureus infection in bone cells: in vitro

“…A sigmoidal growth curve was determined which explains the feasibility of growing S. aureus in DMEM cell culture media. S. aureus co-culture with host cells and its growth in animal cell culture media has been studied earlier [23,24].…”

Oral hygiene might prevent cancer

“…Fusobacterium nucleatum is also an important periodontal pathogen present in the bacterial complexity involved in the development of the biofilms [ 54 , 121 ] and in the locally orchestrated immune responses of the gingival fibroblasts, the first line of defense against oral microorganisms [121] . Likewise, in infected oral epithelial cells, Porphyromonas gingivalis activates NFκB and MAPK pathways [122] and the growth and adherence of Staphylococcus aureus are enhanced through the PGE2 produced by the activated COX-2/PGE2 axe [123] . S. aureus , as well as other strains previously thought to be non-producers of biofilms, are always associated with biofilm producer bacteria in this type of polymicrobial colonization [124] .…”

“…S. aureus , as well as other strains previously thought to be non-producers of biofilms, are always associated with biofilm producer bacteria in this type of polymicrobial colonization [124] . Interestingly, aspirin and other NSAIDs are efficient inhibitors of biofilm formation [ 125 , 126 , 127 , 128 , 129 ] and may control periodontitis though the inhibition of the gingival tissue microbioma-related inflammation [ 74 , 130 , 131 ], as in the examples cited above [ 122 , 123 ]. Resveratrol and its glycosylated derivative THSG [113] have been, intriguingly, proposed for possible complementary treatments for periodontitis through their inhibition of Porphyromonas gingivalis -induced inflammatory responses in human gingival fibroblasts [132] .…”