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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

Dose response to LPS in Duoxa+/+ and Duoxa-/- mice.Leukocytes were collected from the airway compartment by BAL 24 hours after intratrachael instillation of LPS (1μg or 10μg). The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control (open box), 1μg LPS (gray box), or 10μg LPS for both Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Data represent mean ± SEM from six animals in each group; * = p<0.05 compared to PBS control.
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pone.0131810.g001: Dose response to LPS in Duoxa+/+ and Duoxa-/- mice.Leukocytes were collected from the airway compartment by BAL 24 hours after intratrachael instillation of LPS (1μg or 10μg). The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control (open box), 1μg LPS (gray box), or 10μg LPS for both Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Data represent mean ± SEM from six animals in each group; * = p<0.05 compared to PBS control.

Mentions: We evaluated live cell count dose responses to 1μg or 10μg LPS between Duoxa-/- and Duoxa+/+ mice (Fig 1). Both Duoxa-/- and Duoxa+/+ mice had robust increases in live cell counts after LPS instillation compared to PBS control. However, there appeared to be no dose response between the two doses of LPS we utilized. Given the lack of statistical significance in cell counts between the two doses, we utilized the 1μg dose of LPS for the remainder of our experiments.


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

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

Dose response to LPS in Duoxa+/+ and Duoxa-/- mice.Leukocytes were collected from the airway compartment by BAL 24 hours after intratrachael instillation of LPS (1μg or 10μg). The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control (open box), 1μg LPS (gray box), or 10μg LPS for both Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Data represent mean ± SEM from six animals in each group; * = p<0.05 compared to PBS control.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493023&req=5

pone.0131810.g001: Dose response to LPS in Duoxa+/+ and Duoxa-/- mice.Leukocytes were collected from the airway compartment by BAL 24 hours after intratrachael instillation of LPS (1μg or 10μg). The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control (open box), 1μg LPS (gray box), or 10μg LPS for both Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Data represent mean ± SEM from six animals in each group; * = p<0.05 compared to PBS control.
Mentions: We evaluated live cell count dose responses to 1μg or 10μg LPS between Duoxa-/- and Duoxa+/+ mice (Fig 1). Both Duoxa-/- and Duoxa+/+ mice had robust increases in live cell counts after LPS instillation compared to PBS control. However, there appeared to be no dose response between the two doses of LPS we utilized. Given the lack of statistical significance in cell counts between the two doses, we utilized the 1μg dose of LPS for the remainder of our experiments.

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