Genetic background modulates outcome of therapeutic amyloid peptides in treatment of neuroinflammation.
Amyloid hexapeptide molecules are effective in the treatment of the murine model of neuroinflammation, known as experimental autoimmune encephalomyelitis (EAE). Efficacy however differs between two inbred mouse strains, C57BL/6J (B6) and C57BL/10SnJ (B10). Amyloid hexapeptide treatments improved the clinical outcomes of B6, but not B10 mice, indicating that genetic background influences therapeutic efficacy. Moreover, although previous studies indicated that prion protein deficiency results in more severe EAE in B6 mice, we observed no such effect in B10 mice. In addition, we found that amyloid hexapeptide treatments of B10 and B6 mice elicited differential IL4 responses. Thus, the modulatory potential of prion protein and related treatments with other amyloid hexapeptides in EAE depends on mouse strain.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. Electronic address: allison.kraus@nih.gov.
Allison
A
Kraus
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Brent
B
Race
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Katie
K
Phillips
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Clayton
C
Winkler
Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Greg
G
Saturday
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michael
M
Kurnellas
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jonathan B
JB
Rothbard
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Bradley R
BR
Groveman
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lawrence
L
Steinman
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Byron
B
Caughey
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004804:Eosinophils / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D000068617:Genetic Background; D015847:Interleukin-4 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009000:Monocytes / Q000473:pathology / Q000648:ultrastructure; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000627:therapeutic use* / Q000633:toxicity; D000072002:Prion Proteins / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D000072002:Prion Proteins; C512657:Prnp protein, mouse; C075222:amyloid beta-protein (1-42); C445081:myelin oligodendrocyte glycoprotein (35-55); D016875:tau Proteins; D015847:Interleukin-4
Amyloid; Experimental autoimmune encephalomyelitis; Prion protein