The role of hyaluronic acid in SEB-induced acute lung inflammation

Uchakina, Olga N.; Castillejo, Clara Miluska; Bridges, Christy C.; McKallip, Robert J.

doi:10.1016/j.clim.2012.11.002

Cited by 18 publications

(23 citation statements)

References 40 publications

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“…Furthermore, previous results from our laboratory demonstrated that SEB exposure leads to increased production of HA in the lungs and in separate studies we demonstrated an important role of CD44 in lymphocyte activation-induced cell death (AICD), suggesting the possibility that SEB-induced HA production may protect immune cells from apoptosis through binding CD44 [2,13]. This possibility is further supported by other studies that demonstrated a protective role of CD44 in lymphocyte survival [17,18].…”

Section: Resultsmentioning

confidence: 68%

“…It has been reported that 4-MU can reduce hyaluronic acid production through inhibition of the mRNA expression of hyaluronic acid synthases or through the depletion of UDP-GlcUA which are essential for HA synthesis [13,19,20,21]. In the current study we examined whether treatment with 4-MU had any effect on the hyaluronic acid synthase expression (HAS) or soluble HA levels in the lungs of SEB-exposed mice.…”

Section: Resultsmentioning

confidence: 97%

“…Previously, we reported that exposure to SEB led to an increase in the levels of soluble HA in the lungs of mice and that treatment with a HA blocking peptide could protect mice from SEB-induced lung injury [13]. It has been reported that 4-MU can reduce hyaluronic acid production through inhibition of the mRNA expression of hyaluronic acid synthases or through the depletion of UDP-GlcUA which are essential for HA synthesis [13,19,20,21].…”

Section: Resultsmentioning

confidence: 99%

“…In recent work examining a possible role of HA in SEB-induced vascular damage we revealed that following SEB exposure, there was an increase in the level of HA in the lungs and that treatment with a HA blocking peptide led to a significant reduction in SEB-induced lung injury [13]. In the current study, we tested the hypothesis that inhibition of hyaluronic acid production will lead to a reduction in lung inflammation following exposure to SEB.…”

Section: Introductionmentioning

confidence: 87%

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Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

McKallip

Uchakina

2013

Toxins

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Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

See 2 more Smart Citations

Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

McKallip

Uchakina

2013

Toxins

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“…Even though most of the initial phase of SEB toxicity (the 'cytokine storm') seemed to be inhibited in severely stressed RASP cadets, functional interaction networks and pathways suggestive of remnants of SEB-induced sepsis or toxic shock 24 (such as activated hypoxia 25 and vascular leakage, integrin activation, 26 angiotensin maturation and TGF-beta receptor signaling and inhibited platelet activation, coagulation, glucocorticoid receptor signaling and cellular adhesion) persisted in both the pre-and post-RASP leukocytes (Supplementary Figure S12). But these may not translate to phenotypic manifestations of sepsis or toxic shock owing to the inhibited inflammatory response that are responsible for SEB-induced sepsis or toxic shock.…”

Section: Discussionmentioning

confidence: 99%

Stress-caused anergy of leukocytes towards Staphylococcal enterotoxin B and exposure transcriptome signatures

et al. 2015

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Leucocytes from soldiers exposed to battlefield-like stress (RASP: Rangers Assessment and Selection Program) were exposed in vitro to Staphylococcal enterotoxin B (SEB). We assayed SEB-induced regulation of gene expression, both in the presence and absence of severe stress, to generate two sets of gene profiles. One set of transcripts and microRNAs were specific to post-RASP SEB exposure, and another set were signatures of SEB exposure common to both the pre- and post-RASP leucocytes. Pathways and upstream regulatory analyses indicated that the post-RASP SEB-signature transcripts were manifestation of the anergic state of post-RASP leucocytes. These were further verified using expression-based predictions of cellular processes and literature searches. Specificity of the second set of transcripts to SEB exposure was verified using machine-learning algorithms on our and four other (Gene Expression Omnibus) data sets. Cell adhesion, coagulation, hypoxia and vascular endothelial growth factor-mediated vascular leakage were SEB-specific pathways even under the background of severe stress. Hsa-miR-155-3p was the top SEB exposure predictor in our data set, and C-X-C motif chemokine ligand 9 was SEB specific in all the analyzed data sets. The SEB-signature transcripts (which also showed distinct expression signatures from Yersinia pestis and dengue virus) may serve as potential biomarkers of SEB exposure even under the background of stress.

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Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses LPS-Induced Lung Inflammation

2014

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Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation. Culturing LPS-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production, and an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from LPS-induced lung injury. Specifically, 4-MU treatment led to a reduction in LPS-induced hyaluronic acid synthase (HAS) messenger RNA (mRNA) levels, reduction in lung permeability, and reduction in proinflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target HA production may be an effective treatment for the inflammatory response following exposure to LPS.

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The role of hyaluronic acid in SEB-induced acute lung inflammation

Cited by 18 publications

References 40 publications

Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

Stress-caused anergy of leukocytes towards Staphylococcal enterotoxin B and exposure transcriptome signatures

Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses LPS-Induced Lung Inflammation

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