Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with chronically inhaled endotoxin

Stavros Garantziotis, David M. Brass, Jordan Savov, John W. Hollingsworth, Erin McElvania-TeKippe, Katie Berman, Julia K L Walker, David A. Schwartz

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Endotoxin (LPS), a Gram-negative cell wall component, has potent proinflammatory properties. Acute LPS exposure causes airway inflammation; chronic exposure causes airway hyperreactivity and remodeling. IL-10 is an important antiinflammatory cytokine, which is decreased in patients with airway disease, such as asthma and cystic fibrosis. To examine the physiologic and therapeutic role of IL-10 in acute and chronic LPS-induced airway disease. Mice were exposed to aerosolized LPS once or daily for 4 wk. Endpoints were airway inflammation, airway reactivity to methacholine, extracellular matrix protein expression, and histologic analysis. IL-10-deficient mice developed significantly enhanced airway cellularity and remodeling when compared with C57BL/6 mice after chronic LPS inhalation. However they demonstrated less airway hyperreactivity associated with higher inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and lung lavage fluid nitrite levels. In a bone marrow transplantation model, the IL-10 antiinflammatory effect was dependent on the hematopoietic but not on the parenchymal IL-10 expression. Induced epithelial human IL-10 expression protected from the LPS effects and led to decreased collagen production. IL-10 attenuates chronic LPS-induced airway inflammation and remodeling. Physiologically, the antiinflammatory effect of IL-10 is mediated by hematopoietic cells. Therapeutically, adenovirus-driven expression of human IL-10 in airway epithelia is sufficient for its protective effect on inflammation and remodeling. The role of IL-10 on airway hyperreactivity is complex: IL-10 deficiency protects against LPS-induced hyperreactivity, and is associated with higher eNOS, iNOS, and airway nitrate levels.

Original languageEnglish (US)
Pages (from-to)662-667
Number of pages6
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume35
Issue number6
DOIs
StatePublished - Dec 2006

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Endotoxins
Interleukin-10
Leukocytes
Fibrosis
Airway Remodeling
Inflammation
Anti-Inflammatory Agents
Nitric Oxide Synthase Type II
Methacholine Chloride
Extracellular Matrix Proteins
Bronchoalveolar Lavage Fluid
Cellular Structures
Nitrites
Bone Marrow Transplantation
Inbred C57BL Mouse
Adenoviridae
Cystic Fibrosis
Nitrates
Cell Wall
Inhalation

Keywords

  • Airway hyperreactivity
  • Airway remodeling
  • Endotoxin
  • IL-10

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with chronically inhaled endotoxin. / Garantziotis, Stavros; Brass, David M.; Savov, Jordan; Hollingsworth, John W.; McElvania-TeKippe, Erin; Berman, Katie; Walker, Julia K L; Schwartz, David A.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 35, No. 6, 12.2006, p. 662-667.

Research output: Contribution to journalArticle

Garantziotis, Stavros ; Brass, David M. ; Savov, Jordan ; Hollingsworth, John W. ; McElvania-TeKippe, Erin ; Berman, Katie ; Walker, Julia K L ; Schwartz, David A. / Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with chronically inhaled endotoxin. In: American Journal of Respiratory Cell and Molecular Biology. 2006 ; Vol. 35, No. 6. pp. 662-667.
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