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Rat Alveolar Type II Cells Inhibit Fibroblast Proliferation by Secreting Interleukin-1α That Stimulates Prostaglandin E2 Production by Fibroblasts* FREE TO VIEW

Tianli Pan, PhD; John M. Shannon, PhD; Jay Y. Westcott, MD; Robert J. Mason, MD
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*From the Department of Medicine (Drs. Pan, Westcott, and Mason), National Jewish Medical and Research Center, Denver, CO; and Division of Pulmonary Biology (Dr. Shannon), Children’s Hospital Medical Center, Cincinnati, OH.

Correspondence to: Tianli Pan, PhD, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206

Chest. 2001;120(1_suppl):S30. doi:10.1378/chest.120.1_suppl.S30
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Alveolar type II cells inhibit lung fibroblast proliferation by secreting a factor(s) that stimulates prostaglandin E2 (PGE2) production by fibroblasts. In the present study, we further defined this factor(s) secreted by alveolar type II cells. Human lung fibroblasts were suspended in rat tail collagen and co-cultured with rat type II cells. Media were collected and antagonists added during days 9 to 12 in culture when fibroblast growth inhibition was maximal. Interleukin (IL)-1 receptor antagonist strongly reduced PGE2 concentration in the media. IL-1β was present in the conditioned media (CM), but exogenous rat IL-1β did not stimulate PGE2 production by human fibroblasts. IL-1α was below level of detection in all CM except CM without serum collected from day 9 to 13 (IL-1α = 40.3 ± 12.4 pg/mL), which was also the condition for highest PGE2 levels. Exogenous rat IL-1α–stimulated PGE2 production by human fibroblasts, and on antibody to IL-1α decreased PGE2 levels. Transforming growth factor-β1 was present in CM but did not increase on days 9 to 13. Exogenous human transforming growth factor-β1 did not stimulate PGE2 production by these fibroblasts. Cyclooxygenase-2 and connective tissue growth factor messenger RNA were expressed at higher levels in fibroblasts from the co-cultures, but there were no changes in collagenase 1 and fibronectin. In separate experiments, we could not find stimulation of fibroblast growth by performing to co-cultures under serum-free conditions or with 0.4% serum instead of 10% serum. In our co-culture system, alveolar type II cells inhibit proliferation by secreting IL-1α, and IL-1α stimulates PGE2 production by human lung fibroblasts.

Abbreviations: CM = conditioned media; IL = interleukin; PGE2 = prostaglandin E2

Supported by National Institutes of Health grant HL56556.




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