Inhibition of human neutrophil degranulation by transforming growth factor-beta1.
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)-beta1 produced by endometrial stromal and epithelial cells. We observed that incubation of neutrophils in vitro with TGF-beta1 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-beta1. Inhibition of lactoferrin release by TGF-beta1 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-beta1 was negated by SB-431542, a small molecule inhibitor that specifically blocks the kinase activity of the type I TGF-beta receptor (ALK5) In contrast to lactoferrin release, another important neutrophil function, interleukin (IL)-8 driven chemotaxis, was not affected by TGF-beta1 at 1 pg/ml or 100 pg/ml. We conclude that in tissues of the female reproductive tract, TGF-beta1 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.
Shen
L
L
Department of Immunology and Microbiology, Dartmouth Medical School, Lebanon, NH 03756, USA. lilian.shen@dartmouth.edu
Smith
J M
JM
Shen
Z
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Eriksson
M
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Sentman
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Wira
C R
CR
D001549:Benzamides / Q000494:pharmacology; D015550:Cell Degranulation / Q000276:immunology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004149:Dioxoles / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology*
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D008070:Lipopolysaccharides; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D007781:Lactoferrin