Heat shock protein 60 elicits abnormal response in macrophages of diabetes-prone non-obese diabetic mice

Biochem Biophys Res Commun. 2002 Jun 14;294(3):592-6. doi: 10.1016/S0006-291X(02)00522-3.

Abstract

Heat shock protein 60 (hsp60) is a target antigen in autoimmune diabetes and injections of human hsp60 for tolerance induction were found to protect non-obese diabetic (NOD) mice, an animal model of human type 1 diabetes, from disease development. We tested whether innate immune cells of NOD mice exhibit an abnormal response to extracellular hsp60. Bone marrow derived macrophages (BMM) were grown from NOD, C57BL/6J, non-obese non-diabetic (NON) mice, and NOD-related congenic variants differing in the Idd-3, Idd-10/18, or major histocompatibility complex (MHC) region. Hsp60-stimulated BMM of NOD mice were found to produce high levels of interleukin (IL)-12(p70). The addition of IL-10 downregulated, whereas cyclooxygenase inhibitors elevated, IL-12(p70) production of activated BMM. BMM of NON, NON-NOD-H-2(g7) as well as of NOD-NON-H-2(nbl) mice produced significantly less IL-12(p70) than BMM of NOD mice, indicating that an interaction between the MHC haplotype and non-MHC genes of the NOD mouse is required for hyperresponsiveness to hsp60.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • Chaperonin 60 / immunology
  • Chaperonin 60 / pharmacology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Humans
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Inbred NOD

Substances

  • Chaperonin 60
  • Interleukin-12