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

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.