Characterization of a murine model with arteritis induced by Nod1 ligand, FK565: A comparative study with a CAWS-induced model.
OBJECTIVE
Kawasaki disease (KD) occurs via activation of the innate immune system. Nucleotide oligomerization domain-1 (NOD1) is a pattern recognition receptor regulating the innate immunity. We characterized histopathology of arteritis induced by FK565, a ligand for NOD1, in mice, compared with Candida albicans water-soluble fraction (CAWS)-induced model.


METHODS
Vasculitis was induced by injection of FK565 or CAWS into C57BL6/J mice (n = 9 and n = 11, respectively). At 4 weeks, they were sacrificed, and plasma cytokines and chemokines were measured.


RESULTS
FK565 injection induced vasculitis mainly involving bilateral coronary arteries whereas the aortic root was diffusely affected in CAWS mice. In FK565 animals, the abdominal aorta and its branching arteries also exhibited inflammation with atherosclerosis. IL-1α, IL-1β, IL-5 and RANTES were increased in FK565 group whereas IL-6, IL-13, G-CSF, IFN-γ, and TNF-α were higher in CAWS animals (p < .05 for all variables). The total area of inflammation in FK565 mice appeared to correlate with IL-1β levels (r = 0.71, p = .05).


CONCLUSIONS
Histopathology of FK565-induced model demonstrated 'site-specific' coronary arteritis mimicking KD. This histopathological difference from CAWS model may be due to different cytokine expression profiles.
a Department of Diagnostic Pathology , Nippon Medical School Hospital , Tokyo , Japan.
Ryuji
R
Ohashi
b Department of Pediatrics , Nippon Medical School , Tokyo , Japan.
Ryuji
R
Fukazawa
b Department of Pediatrics , Nippon Medical School , Tokyo , Japan.
Makoto
M
Watanabe
b Department of Pediatrics , Nippon Medical School , Tokyo , Japan.
Koji
K
Hashimoto
b Department of Pediatrics , Nippon Medical School , Tokyo , Japan.
Nobuko
N
Suzuki
c Laboratory for Immunopharmacology of Microbial Products , Tokyo University of Pharmacy and Life Sciences , Tokyo , Japan.
Noriko
N
Nagi-Miura
c Laboratory for Immunopharmacology of Microbial Products , Tokyo University of Pharmacy and Life Sciences , Tokyo , Japan.
Naohito
N
Ohno
d Department of Analytic Human Pathology , Nippon Medical School , Tokyo , Japan.
Akira
A
Shimizu
b Department of Pediatrics , Nippon Medical School , Tokyo , Japan.
Yasuhiko
Y
Itoh
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D002176:Candida albicans / Q000737:chemistry* / Q000276:immunology; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009080:Mucocutaneous Lymph Node Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology / Q000633:toxicity*; D011485:Protein Binding; D013347:Subcellular Fractions / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000276:Adjuvants, Immunologic; D015850:Interleukin-6; D008024:Ligands; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine
Arteritis; Kawasaki disease; Nod1; cytokines; innate immunity