Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice

Academic Article

Abstract

  • In vitro, IL-6 is the main inducer of the human C-reactive protein (CRP) gene, and IL-1 and steroids can enhance this effect. However, in mice, IL-6 is necessary but not sufficient for induction of the human CRP transgene, and testosterone is required for its constitutive expression by males. To examine the relative contributions of testosterone and IL-6 in the regulation of CRP gene expression, we produced CRP-transgenic (CRPtg), IL-6-deficient (IL-6(- /-)) mice. Male CRPtg/IL-6(-/-) mice expressed CRP constitutively, but CRP levels were not increased after injection of LPS. However, acute-phase CRP levels were attained after injection of IL-6. In contrast, female CRPtg/IL- 6(-/-) mice did not express CRP constitutively or after administration of LPS, IL-6, IL-1, or IL-6 pins IL-1. Like males, testosterone-treated CRPtg/IL-6(-/-) females expressed CRP constitutively, and their transgene responded to injection of IL-6. The endogenous acute-phase protein serum amyloid P (SAP) was expressed constitutively equally by male and female IL- 6(-/-) mice, responded minimally to LPS, and did not respond to either IL-6 or IL-1 alone. Acute-phase levels of SAP were induced in IL-6(-/-) mice by injection of IL-6 together with IL-1 or LPS. We conclude that in vivo, both constitutive and IL-6-dependent acute-phase expression of the CRP transgene require testosterone. In contrast, testosterone is not required for expression of the SAP gene, which requires IL-1 plus IL-6 for acute-phase induction.
  • Published In

    Author List

  • Szalai AJ; Van Ginkel FW; Dalrymple SA; Murray R; McGhee JR; Volanakis JE
  • Start Page

  • 5294
  • End Page

  • 5299
  • Volume

  • 160
  • Issue

  • 11