Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.
Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders.
Tang
W
W
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Geba
G P
GP
Zheng
T
T
Ray
P
P
Homer
R J
RJ
Kuhn
C
C
Flavell
R A
RA
Elias
J A
JA
D000402:Airway Obstruction / Q000503:physiopathology*; D000403:Airway Resistance; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D006651:Histocytochemistry; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000235:genetics / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism; D014598:Uteroglobin
D017370:Interleukin-11; D011506:Proteins; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D016210:Methacholine Chloride; D014598:Uteroglobin