Leukemia inhibitory factor (LIF) and LIF receptor in human lung distribution and regulation of LIF release

The distribution and regulation of leukemia inhibitory factor (LIF) and its receptor (LIFR) in human lung tissue is unknown. We recently found that LI F was immunolocalized to several cell types in human airways, and that exog enous LIF modulated neural and contractile responses of explanted airways. The present study aimed to determine the cellular distribution and regulati on of gene transcripts for LIF and LIFR in human lung, and measured the rel ease of LIF in response to anti-immunoglobulin (Ig)E, interleukin (IL)-I be ta, and IL-6. Exposure of human lung to IL-1 beta (100 pg/ml) resulted in t he rapid induction of LIF messenger RNA (mRNA) (1 h) and subsequent protein release (6 h). Similar results were observed when lung tissue was exposed to anti-IgE (6 U/ml). Gene transcripts for LIF were observed in nine pulmon ary cell types, with the greatest expression occurring in fibroblasts. LIFR transcripts were also widely expressed in these cell types. In cultures of nontransformed epithelial cells, lung fibroblasts, and airway smooth-muscl e cells, IL-1 beta (100 pg/ml) induced the rapid accumulation of LIF mRNA a nd protein release, with fibroblasts liberating the greatest amount. IL-6 a lso induced the expression of LIF mRNA and release of LIF in airway smooth- muscle cells, whereas exogenous LIF itself had no effect. Expression of LIF R mRNA was not influenced by exposure to IL-1 beta or LIF in any of the cel l lines used. These results highlight the widespread distribution and rapid release of LIF in human lung tissue and, in conjunction with our previous report, suggest that this cytokine may play an important role in lung infla mmatory processes and neuroimmune interactions.