Interleukin-1beta deficiency results in reduced NF-kappaB levels in pregnant mice.
Interleukin (IL)-1beta-deficient (IL-1beta(-/-)) mice were assessed for cytokine production during pregnancy. A significant reduction in nuclear factor (NF)-kappaB p65 protein content was observed in the uteri and spleens of pregnant IL-1beta(-/-) mice, as demonstrated by immunohistochemistry and Western immunoblot analysis. In addition, electromobility gel shift assay revealed less DNA binding activity of NF-kappaB p65-containing complex in pregnant IL-1beta(-/-) mice. To investigate differences in cytokine production regulated by NF-kappaB, the levels of tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, and interferon-gamma were measured in the uterine wall, spleen homogenates, and spleen cell cultures obtained from pregnant mice. Endocervical administration of lipopolysaccharide (LPS) increased cytokine levels in both wild-type (IL-1beta(+/+)) and IL-1beta(-/-) animals, but in IL-1beta(-/-) mice this response was 50-75% lower. Splenocytes from nonpregnant mice exhibited decreased LPS-induced cytokine production when primed in vitro with progesterone. This suppression was 25% greater in IL-1beta(-/-) than in IL-1beta(+/+) mice. These data suggest that constitutive NF-kappaB p65 protein synthesis is regulated by IL-1beta, particularly during pregnancy.
Reznikov
L L
LL
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. leonid.reznikov@uchsc.edu
Shames
B D
BD
Barton
H A
HA
Selzman
C H
CH
Fantuzzi
G
G
Kim
S H
SH
Johnson
S M
SM
Dinarello
C A
CA
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004586:Electrophoresis; D005260:Female; D007375:Interleukin-1 / Q000172:deficiency*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051996:Transcription Factor RelA; D011374:Progesterone