Inhibition of human neutrophil degranulation by transforming growth factor-β1

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Abstract
Neutrophils enter tissues including the uterus and are found in the endometrium in increased numbers prior to menses. In this environment, they are exposed to transforming growth factor (TGF)-β1 produced by endometrial stromal and epithelial cells. We observed that incubation of neutrophils in vitro with TGF-β1 at 1 pg/ml significantly reduced their secretion of lactoferrin in response to lipopolysaccharide (LPS). This effect was achieved with as little as 15 min of pretreatment with TGF-β1. Inhibition of lactoferrin release by TGF-β1 was observed irrespective of whether neutrophils were stimulated by ligands for Toll-like receptor (TLR)-2, TLR-4 or FPR, the G protein-coupled receptor for formylated peptides. Inhibition by TGF-β1 was negated by SB-431542, a small molecule inhibitor that specifically blocks the kinase activity of the type I TGF-β receptor (ALK5) In contrast to lactoferrin release, another important neutrophil function, interleukin (IL)-8 driven chemotaxis, was not affected by TGF-β1 at 1 pg/ml or 100 pg/ml. We conclude that in tissues of the female reproductive tract, TGF-β1 inhibition of neutrophil degranulation may prevent these cells from initiating an inflammatory response or releasing degradative enzymes that could potentially damage the oocyte or fetus.