Interactions of keratinocyte growth factor with a nitrating species after marrow transplantation in mice

We reported that allogeneic T cells given to irradiated mice at the time of marrow transplantation stimulated tumor necrosis factor (TNF)-alpha, inter feron (IFN)-gamma, and nitric oxide (. NO) production in the lung, and the addition of cyclophosphamide (known to stimulate superoxide production) fav ored the generation of a nitrating species. Although keratinocyte growth fa ctor (KGF) prevents experimental lung injury by promoting epithelial repair , its effects on the production of inflammatory mediators has not been stud ied. KGF given before transplantation inhibited the T cell-induced increase in bronchoalveolar lavage fluid protein, TNF-alpha, IFN-gamma, and nitrite levels measured on day 7 after transplantation without modifying cellular infiltration or proinflammatory cytokines and inducible . NO synthase mRNA. KGF also suppressed . NO production by alveolar macrophages obtained from mice injected with T cells. In contrast, the same schedule of KGF failed to prevent permeability edema or suppress TNF-alpha, IFN-gamma, and . NO prod uction in mice injected with both T cells and cyclophosphamide. Because onl y epithelial cells respond to KGF, these data are consistent with the produ ction of an epithelial cell-derived mediator capable of downregulating macr ophage function. However, the presence of a nitrating agent impairs KGF-der ived responses.