Growth hormone increases lung microvascular injury in lipopolysaccharide peritonitis rats: possible involvement of NF-kappaB activation in circulating neutrophils.
Abstract
AIM: To investigate the effects of growth hormone (GH) on NF-kappaB activity in
neutrophils and neutrophils-mediated organ injury induced by lipopolysaccharide
(LPS) in rats.
METHODS: Male Wistar rats challenged with or without LPS (5 mg/kg) were treated
with varied doses of GH (0.5, 1.0, and 2.0 mg/kg) for 2 or 4 h. NF-kappaB
activities in circulating neutrophils were measured with electrophoretic mobility
shift assays (EMSA), and I-kappaB levels in circulating neutrophils were detected
by Western blot. Lung neutrophils sequestration and lung microvascular
permeability were measured at 4 h after LPS challenge.
RESULTS: Circulating neutrophils in LPS challenged rats had increased NF-kappaB
activity and decreased I-kappaB level as compared with controls. GH dramatically
increased NF-kappaB activity and I-kappaB degradation induced by LPS challenge in
neutrophils. Also, subsequently, GH treatment increased lung neutrophils
sequestration and lung microvascular injury induced by LPS.
CONCLUSION: These results suggest that treatment of GH is harmful, instead of
beneficial, to LPS-induced organ injury. Increased neutrophils' NF-kappaB
activity and lung neutrophils sequestration are critical in vivo mechanisms
mediating GH action on LPS-induced organ injury.
Keywords:
neutrophils and neutrophils-mediated organ injury induced by lipopolysaccharide
(LPS) in rats.
METHODS: Male Wistar rats challenged with or without LPS (5 mg/kg) were treated
with varied doses of GH (0.5, 1.0, and 2.0 mg/kg) for 2 or 4 h. NF-kappaB
activities in circulating neutrophils were measured with electrophoretic mobility
shift assays (EMSA), and I-kappaB levels in circulating neutrophils were detected
by Western blot. Lung neutrophils sequestration and lung microvascular
permeability were measured at 4 h after LPS challenge.
RESULTS: Circulating neutrophils in LPS challenged rats had increased NF-kappaB
activity and decreased I-kappaB level as compared with controls. GH dramatically
increased NF-kappaB activity and I-kappaB degradation induced by LPS challenge in
neutrophils. Also, subsequently, GH treatment increased lung neutrophils
sequestration and lung microvascular injury induced by LPS.
CONCLUSION: These results suggest that treatment of GH is harmful, instead of
beneficial, to LPS-induced organ injury. Increased neutrophils' NF-kappaB
activity and lung neutrophils sequestration are critical in vivo mechanisms
mediating GH action on LPS-induced organ injury.