Inhibition of human neutrophil degranulation by transforming growth factor‐β1

Summary 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.