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Am J Physiol Regul Integr Comp Physiol 278: R263-R270, 2000;
0363-6119/00 $5.00
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Vol. 278, Issue 1, R263-R270, January 2000

Interleukin-1beta deficiency results in reduced NF-kappa B levels in pregnant mice

Leonid L. Reznikov1, Brian D. Shames2, Hazel A. Barton2, Craig H. Selzman2, Giamila Fantuzzi1, Soo-Hyun Kim1, Sylene M. Johnson2, and Charles A. Dinarello1

1 Division of Infectious Diseases and 2 Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262

Interleukin (IL)-1beta -deficient (IL-1beta -/-) mice were assessed for cytokine production during pregnancy. A significant reduction in nuclear factor (NF)-kappa B 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-kappa B p65-containing complex in pregnant IL-1beta -/- mice. To investigate differences in cytokine production regulated by NF-kappa B, 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-kappa B p65 protein synthesis is regulated by IL-1beta , particularly during pregnancy.

p65 nuclear factor-kappa B; lipopolysaccharide; inflammation


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