RGD Reference Report - Administration of ricin induces a severe inflammatory response via nonredundant stimulation of ERK, JNK, and P38 MAPK and provides a mouse model of hemolytic uremic syndrome.

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Administration of ricin induces a severe inflammatory response via nonredundant stimulation of ERK, JNK, and P38 MAPK and provides a mouse model of hemolytic uremic syndrome.
Authors:	Korcheva, V Wong, J Corless, C Iordanov, M Magun, B
Citation:	Korcheva V, etal., Am J Pathol. 2005 Jan;166(1):323-39.
RGD ID:	7242276
Pubmed:	PMID:15632024 (View Abstract at PubMed)
PMCID:	PMC1602309 (View Article at PubMed Central)
DOI:	DOI:10.1016/S0002-9440(10)62256-0 (Journal Full-text)
Recent interest in the health consequences of ricin as a weapon of terrorism has led us to investigate the effects of ricin on cells in vitro and in mice. Our previous studies showed that depurination of the 28S rRNA by ricin results in the inhibition of translation and the coordinate activation of the stress-activated protein kinases JNK and p38 MAPK. In RAW 264.7 macrophages, ricin induced the activation of ERK, JNK, and p38 MAPK, the accumulation of mRNA encoding tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, the transcription factors c-Fos, c-Jun, and EGR1, and the appearance of TNF-alpha protein in the culture medium. Using specific inhibitors of MAPKs, we demonstrated the nonredundant roles of the individual MAPKs in mediating proinflammatory gene activation in response to ricin. Similarly, the intravenous administration of ricin to mice led to the activation of ERK, JNK, and p38 MAPK in the kidneys, and increases in plasma-borne TNF-alpha, IL-1beta, and IL-6. Ricin-injected mice developed the hallmarks of hemolytic uremic syndrome, including thrombotic microangiopathy, hemolytic anemia, thrombocytopenia, and acute renal failure. Microarray analyses demonstrated a massive proinflammatory transcriptional response in the kidneys, coincidental with the symptoms of hemolytic uremic syndrome. Therapeutic management of the inflammatory response may affect the outcome of intoxication by ricin.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
hemolytic-uremic syndrome		ISO	Fos (Mus musculus)	7242276; 7242276		RGD
hemolytic-uremic syndrome		IEP		7242276		RGD

Objects Annotated

Genes (Rattus norvegicus)

Fos (Fos proto-oncogene, AP-1 transcription factor subunit)

Genes (Mus musculus)

Fos (FBJ osteosarcoma oncogene)

Genes (Homo sapiens)

FOS (Fos proto-oncogene, AP-1 transcription factor subunit)

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Administration of ricin induces a severe inflammatory response via nonredundant stimulation of ERK, JNK, and P38 MAPK and provides a mouse model of hemolytic uremic syndrome.