Lipoteichoic Acid-Induced Nitric Oxide Production Depends on the Activation of Platelet-Activating Factor Receptor and Jak2

Han, Seung Hyun; Kim, Je Hak; Seo, Ho Seong; Martin, Michael; Chung, Gook-Hyun; Michalek, Suzanne M.; Nahm, Moon H.

doi:10.4049/jimmunol.176.1.573

Cited by 46 publications

(15 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TLR2 agonists poorly induce IFN-β. LTA in particular did not induce IFN-β expression [66]. By contrast, the LPS-induced TLR4 signaling cascade comprises two pathways: a MyD88-pathway with rapid activation of NF-κB and MAPK, and a MyD88-independent pathway leading to the induction of IFN-inducible genes [67].…”

Section: Discussionmentioning

confidence: 99%

“…A good example of an IFN-dependent gene is Nos2 , because full transcriptional induction of the Nos2 gene encoding the inducible nitric oxide synthase (iNOS) requires type I IFN signaling and additional signals emanating from pattern recognition receptors [68,69]. Up-regulation of Nos2 by staphylococcal LTA occurs, driven by the stimulation of the receptor for the platelet activating factor (PAFR) [66], but LTA did not activate PAFR on bMEC [33]. This is consistent with our observation that Nos2 was much more differentially expressed by LPS-stimulated than by SaS-stimulated MEC (Figure 5c).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system

Gilbert

Cunha

Jensen

et al. 2013

Vet Res

179

161

View full text Add to dashboard Cite

Mastitis caused by Escherichia coli and Staphylococcus aureus is a major pathology of dairy cows. To better understand the differential response of the mammary gland to these two pathogens, we stimulated bovine mammary epithelial cells (bMEC) with either E. coli crude lipopolysaccharide (LPS) or with S. aureus culture supernatant (SaS) to compare the transcriptomic profiles of the initial bMEC response. By using HEK 293 reporter cells for pattern recognition receptors, the LPS preparation was found to stimulate TLR2 and TLR4 but not TLR5, Nod1 or Nod2, whereas SaS stimulated TLR2. Biochemical analysis revealed that lipoteichoic acid, protein A and α-hemolysin were all present in SaS, and bMEC were found to be responsive to each of these molecules. Transcriptome profiling revealed a core innate immune response partly shared by LPS and SaS. However, LPS induced expression of a significant higher number of genes and the fold changes were of greater magnitude than those induced by SaS. Microarray data analysis suggests that the activation pathways and the early chemokine and cytokine production preceded the defense and stress responses. A major differential response was the activation of the type I IFN pathway by LPS but not by SaS. The higher upregulation of chemokines (Cxcl10, Ccl2, Ccl5 and Ccl20) that target mononuclear leucocytes by LPS than by SaS is likely to be related to the differential activation of the type I IFN pathway, and could induce a different profile of the initial recruitment of leucocytes. The MEC responses to the two stimuli were different, as LPS was associated with NF-κB and Fas signaling pathways, whereas SaS was associated with AP-1 and IL-17A signaling pathways. It is noteworthy that at the protein level secretion of TNF-α and IL-1β was not induced by either stimulus. These results suggest that the response of MEC to diffusible stimuli from E. coli and S. aureus contributes to the onset of the response with differential leucocyte recruitment and distinct inflammatory and innate immune reactions of the mammary gland to infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system

Gilbert

Cunha

Jensen

et al. 2013

Vet Res

179

161

View full text Add to dashboard Cite

show abstract

“…Enterococcus faecalis LTA can induce the expression of IL-6, IL-1β, TNF-α, and other inflammatory factors (Baik et al, 2008;Lu et al, 2015;Park, Han, et al, 2013) and can inhibit the proliferation and induce apoptosis of human osteoblast-like MG63 cells (Tian et al, 2013). Staphylococcus aureus LTA promoted NO activation by JAK2 (Han et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

JAK2‐STAT3 signaling pathway is involved in rat periapical lesions induced by Enterococcus faecalis

Wang

Jin

et al. 2019

Oral Diseases

View full text Add to dashboard Cite

Objectives This study aimed to investigate the role of JAK2‐STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) in periapical disease caused by Enterococcus faecalis, as well as the correlation between lipoteichoic acid (LTA) in E. faecalis and the activity of the JAK2‐STAT3 signaling pathway and osteoclast formation. Materials and Methods A rat model of periapical periodontitis induced by E. faecalis was established. Periapical bone resorption was confirmed by HE staining. The expression of JAK2, p‐JAK2, STAT3, and p‐STAT3 was assessed with immunohistochemical staining. Osteoclasts were observed through enzyme histochemical staining. LTA acted on mouse osteoclast precursor cells (RAW264.7 cells); a JAK2 inhibitor (AG490) was used to inhibit the JAK2‐STAT3 pathway in RAW264.7 cells. The expression of proteins in the JAK2‐STAT3 pathway and TRAP (tartrate resistant acid phosphatase) in RAW264.7 cells was also detected. Results Rat periapical periodontitis was successfully established and bone resorption peaked at day 21. The expression of critical components in the JAK2‐STAT3 pathway increased with the progression of inflammation. LTA promoted the differentiation of RAW264.7 cells into osteoclasts. NFATc1 was highly expressed and was inhibited by AG490. Conclusions JAK2‐STAT3 signaling pathway plays an important role in the process of periapical bone resorption and osteoclastogenesis.

show abstract

“…In contrast, we found no change in nitrite levels in the present study after exposure to killed gram-positive bacteria. Gram-positive bacteria can also acutely induce NO production via lipoteichoic acid (24), but the long-term effects are unclear. It is important to note that, in term fetal sheep, LPS injection was associated with a transient increase in total nitrite/nitrate only after the first bolus of LPS, with no change after subsequent boluses even though transient vasodilation still occurred (17).…”

Section: Discussionmentioning

confidence: 99%

The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep

Cowie¹,

Stone²,

Barrett³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the neural and cardiovascular effects of OK-432 in preterm fetal sheep (104 +/- 1 days, term 147 days). OK-432 (0.1 mg, n = 6) or saline vehicle (n = 7) was infused in the fetal pleura, and fetuses were monitored for 7 days. Blood samples were taken routinely for plasma nitrite measurement. Fetal brains were taken for histological assessment at the end of the experiment. Between 3 and 7 h postinjection, OK-432 administration was associated with transient suppression of fetal body and breathing movements and electtroencephalogram activity (P < 0.05), increased carotid and femoral vascular resistance (P < 0.05), but no change in blood pressure. Brain activity and behavior then returned to normal except in one fetus that developed seizures. OK-432 fetuses showed progressive, sustained vasodilatation (P < 0.05), with lower blood pressure after 4 days (P < 0.05), but normal heart rate. There were no changes in plasma nitrite levels. Histological studies showed bilateral infarction in the dorsal limb of the hippocampus of the fetus that developed seizures, but no injury in other fetuses. We conclude that a single low-dose injection of OK-432 can be associated with risk of focal cerebral injury in the preterm fetus and chronic central and peripheral vasodilatation that does not appear to be mediated by nitric oxide.

show abstract

Lipoteichoic Acid-Induced Nitric Oxide Production Depends on the Activation of Platelet-Activating Factor Receptor and Jak2

Cited by 46 publications

References 65 publications

Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system

Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system

JAK2‐STAT3 signaling pathway is involved in rat periapical lesions induced by Enterococcus faecalis

The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep

Contact Info

Product

Resources

About