Effects of interleukin-1 beta on DNA synthesis in rat alveolar type II cells in primary culture.
Proliferation of alveolar type II cells is critical for restoration of the integrity of alveolar epithelium in alveolar injuries caused by a number of different aetiologies. Because effects of inflammatory cytokines on the proliferation of alveolar type II cells are not clear, we investigated the effects of interleukin-1 beta (IL-1 beta) on [3H]-thymidine incorporation into DNA in rat alveolar type II cells in primary culture. Interleukin-1 beta enhanced the [3H]-thymidine incorporation dose and time dependently. The increase of [3H]-thymidine incorporation was observed in parallel with increased number of rat alveolar type II cells. The effect of IL-1 beta on [3H]-thymidine incorporation was additive to effects of growth factors which were known to act as mitogenic factors for type II cells. Anti-interleukin-1 beta antibody or IL-1 receptor antagonist partially inhibited the effects of IL-1 beta on [3H]-thymidine incorporation. Their combination completely inhibited the effects of IL-1 beta. In the absence of IL-1 beta, the combination inhibited the [3H]-thymidine incorporation to a level under that in the control. Isolated alveolar type II cells were immunocytochemically stained positive with anti-IL-1 beta antibody. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed the presence of the mRNA for IL-1 beta in cultured alveolar type II cells. These results demonstrate that exogenous IL-1 beta stimulates DNA synthesis in alveolar type II cells and that the cells also produce IL-1 beta endogenously and suggest that endogenous IL-1 beta may mediate basal DNA synthesis of alveolar type II cells.
Yang
G H
GH
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Osanai
K
K
Takahashi
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology* / Q000502:physiology*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000293:injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine; D013997:Time Factors
D007375:Interleukin-1; D013936:Thymidine