In vitro and in vivo effects of genistein on murine alveolar macrophage TNF alpha production.
The present study was performed to determine whether genistein could inhibit in vivo LPS-induced alveolar macrophage TNFalpha production and thus reduce the alveolar neutrophil influx following LPS. In vitro incubation with genistein completely inhibited LPS-induced TNFalpha production by alveolar macrophages (AM) from BALB/c mice. Subsequently mice were pretreated with intraperitoneal genistein or vehicle, then received nasal LPS to induce an alveolitis. Genistein was then administered every eight hours for five days following LPS. At 24 hours after LPS, the bronchoalveolar lavage (BAL) TNFalpha and ex vivo TNFalpha production from AM, were lower in the genistein treated animals. As well, total BAL white blood cell (WBC) count was reduced in the genistein as compared to the vehicle-only group. The percent neutrophils and the resolution of neutrophils were similar between genistein and vehicle groups. Therefore, genistein was able to decrease AM TNFalpha production, and was associated with a decrease in BAL WBC count post-LPS.
College of Medicine, Department of Medicine University of Kentucky, Lexington 40536-0084, USA.
P E
PE
Morris
L E
LE
Olmstead
A E
AE
Howard-Carroll
G R
GR
Dickens
M L
ML
Goltz
C
C
Courtney-Shapiro
P
P
Fanti
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha; D019833:Genistein