Induced eosinophilia and proliferation in Angiostrongylus cantonensis-infected mouse brain are associated with the induction of JAK/STAT1, IAP/NF-kappaB and MEKK1/JNK signals.
Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand, and Japan. Although eosinophilia is an important clinical manifestation of A. cantonensis infection, the role of eosinophils in the progress of the infection remains to be elucidated. In this experiment, we show that A. cantonensis-induced eosinophilia and inflammation might lead to the induction of IAP/NF-kappaB, JAK/STAT1 and MEKK1/JNK signals. The phosphorylation levels of JAK and JNK, STAT1, IAP, NF-kappaB and MEKK1 protein products were significantly increased after 12 days or 15 days of A. cantonensis infection. However, no significant differences in MAPKs such as Raf, MEK-1, ERK1/2 and p38 expression were found between control and infected mice. The activation potency of JAK/STAT1, IAP/NF-kappaB and MEKK1/JNK started increasing on day 3, with significant induction on day 12 or day 15 after A. cantonensis infection. Consistent results were noted in the pathological observations, including eosinophilia, leukocyte infiltration, granulomatous reactions, and time responses in the brain tissues of infected mice. These data suggest that the development of brain injury by eosinophilia of A. cantonensis infection is associated with activation of JAK/STAT1 signals by cytokines, and/or activation of MEKK1/JNK by oxidant stress, and/or activation of NF-kappaB by increasing IAP expression.
Lan
K P
KP
Department of Parasitology, Chung Shan Medical University, 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan.
Wang
C J
CJ
Hsu
J D
JD
Chen
K M
KM
Lai
S C
SC
Lee
H H
HH
D017185:Angiostrongylus cantonensis; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001923:Brain Chemistry; D001927:Brain Diseases / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004802:Eosinophilia / Q000378:metabolism / Q000469:parasitology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053613:Janus Kinase 1; D048670:MAP Kinase Kinase 4; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D018384:Oxidative Stress; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D017206:Strongylida Infections / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; C030193:immunosuppressive acidic protein; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases