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Original Research: OBSTRUCTIVE LUNG DISEASES |

Dapsone Inhibits IL-8 Secretion From Human Bronchial Epithelial Cells Stimulated With Lipopolysaccharide and Resolves Airway Inflammation in the FerretDapsone Inhibits IL-8

Soichiro Kanoh, MD, PhD; Tsuyoshi Tanabe, MD, PhD; Bruce K. Rubin, MD, FCCP
Author and Funding Information

From the Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA.

Correspondence to: Bruce K. Rubin, MD, FCCP, Office of the Chairman, Department of Pediatrics, 1001 E Marshall St, Virginia Commonwealth University School of Medicine, Richmond, VA 23298; e-mail: brubin@vcu.edu


Funding/Support: This research was funded by Virginia Commonwealth University and National Defense Medical College (Japan) internal finds.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(4):980-990. doi:10.1378/chest.10-2908
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Background:  IL-8 is an important activator and chemoattractant for neutrophils that is produced by normal human bronchial epithelial (NHBE) cells through mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 pathways. Dapsone, a synthetic sulfone, is widely used to treat chronic neutrophil dermatoses. We investigated the effects of dapsone on polarized IL-8 secretion from lipopolysaccharide (LPS)-stimulated NHBE cells and further evaluated its ability to decrease LPS-induced inflammation in the ferret airway.

Methods:  NHBE cells were grown at air-liquid interface (ALI) to ciliated differentiation. Baseline and endotoxin (LPS)-stimulated IL-8 secretion was measured by enzyme-linked immunosorbent assay at air and basal sides with and without dapsone. Western blotting was used to determine signaling pathways. In vivo, ferrets were exposed to intratracheal LPS over a period of 5 days. Once inflammation was established, oral or nebulized dapsone was administered for 5 days. Intraepithelial neutrophil accumulation was analyzed histologically, and mucociliary transport was measured on the excised trachea.

Results:  Dapsone, 1 μg/mL, did not influence unstimulated (basal) IL-8 secretion. Apical LPS stimulation induced both apical and basolateral IL-8, but basolateral LPS increased only basolateral IL-8. Dapsone inhibited polarized IL-8 secretion from ALI-conditioned cells. Dapsone also decreased LPS-induced IL-8 mRNA level. LPS led to phosphorylation of extracellular signal-regulated kinase 1/2, but not p38 MAPK or c-Jun NH2-terminal kinase. LPS also induced NF-κB p65 phosphorylation, an effect that was inhibited by dapsone. Both oral and aerosol dapsone decreased LPS-induced intraepithelial neutrophil accumulation, but only treatment with aerosol dapsone restored mucociliary transport to normal.

Conclusions:  Dapsone, given either systemically or as an aerosol, may be useful in treating neutrophilic airway inflammation.

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