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DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways.

Chang S, Linderholm A, Harper R - PLoS ONE (2015)

Bottom Line: We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h.Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups.These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, California 95616, United States.

ABSTRACT
Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS-induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h. Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

No MeSH data available.


Related in: MedlinePlus

Time course of LPS-induced airway inflammation.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control and LPS-exposed Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice as indicated. Data are shown as mean ± SEM for six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.
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pone.0131810.g002: Time course of LPS-induced airway inflammation.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control and LPS-exposed Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice as indicated. Data are shown as mean ± SEM for six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.

Mentions: To evaluate the LPS-induced influx of inflammatory cells in the lung over time, total live cell counts were analyzed and compared between Duoxa-/- and Duoxa+/+ mice at 3h, 6h, 24h, and 7 days (Fig 2). Both Duoxa-/- and Duoxa+/+ mice demonstrated increasing live cell counts at each timepoint up to 24h which subsided at 7 days. While Duoxa-/- and Duoxa+/+ mice had similar trends in live cell counts for all timepoints, Duoxa-/- mice had significantly increased live cell counts at 24h when compared to Duoxa+/+ mice (p ≤0.05).


DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways.

Chang S, Linderholm A, Harper R - PLoS ONE (2015)

Time course of LPS-induced airway inflammation.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control and LPS-exposed Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice as indicated. Data are shown as mean ± SEM for six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493023&req=5

pone.0131810.g002: Time course of LPS-induced airway inflammation.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control and LPS-exposed Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice as indicated. Data are shown as mean ± SEM for six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.
Mentions: To evaluate the LPS-induced influx of inflammatory cells in the lung over time, total live cell counts were analyzed and compared between Duoxa-/- and Duoxa+/+ mice at 3h, 6h, 24h, and 7 days (Fig 2). Both Duoxa-/- and Duoxa+/+ mice demonstrated increasing live cell counts at each timepoint up to 24h which subsided at 7 days. While Duoxa-/- and Duoxa+/+ mice had similar trends in live cell counts for all timepoints, Duoxa-/- mice had significantly increased live cell counts at 24h when compared to Duoxa+/+ mice (p ≤0.05).

Bottom Line: We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h.Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups.These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, California 95616, United States.

ABSTRACT
Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS-induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h. Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

No MeSH data available.


Related in: MedlinePlus