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.
Adler
Thure
T
German Diabetes Research Institute at the Heinrich-Heine-University, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany.
Akiyama
Hidehiko
H
Herder
Christian
C
Kolb
Hubert
H
Burkart
Volker
V
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D018834:Chaperonin 60 / Q000276:immunology / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD
D018834:Chaperonin 60; D018664:Interleukin-12