Document Details

Document Type : Article In Journal 
Document Title :
IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice
IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice
 
Document Language : English 
Abstract : Intestinal damage and severe diarrhea are serious side effects of cancer chemotherapy and constrain the usage of most such therapies. Here we show that interleukin-33 (IL-33) mediates the severe intestinal mucositis in mice treated with irinotecan (CPT-11), a commonly used cancer chemotherapeutic agent. Systemic CPT-11 administration led to severe mucosal damage, diarrhea, and body weight loss concomitant with the induction of IL-33 in the small intestine (SI). This mucositis was markedly reduced in mice deficient in the IL-33R (ST2(-/-)). Moreover, recombinant IL-33 exacerbated the CPT-11-induced mucositis, whereas IL-33 blockade with anti-IL-33 antibody or soluble ST2 markedly attenuated the disease. CPT-11 treatment increased neutrophil accumulation in the SI and adhesion to mesenteric veins. Supernatants from SI explants treated with CPT-11 enhanced transmigration of neutrophils in vitro in an IL-33-, CXCL1/2-, and CXCR2-dependent manner. Importantly, IL-33 blockade reduced mucositis and enabled prolonged CPT-11 treatment of ectopic CT26 colon carcinoma, leading to a beneficial outcome of the chemotherapy. These results suggest that inhibition of the IL-33/ST2 pathway may represent a novel approach to limit mucositis and thus improve the effectiveness of chemotherapy. 
ISSN : 1933-0219 
Journal Name : Mucosal immunology 
Volume : 7 
Issue Number : 5 
Publishing Year : 1435 AH
2014 AD 
Article Type : Article 
Added Date : Tuesday, March 15, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
R GuabirabaGuabiraba, R Investigator  
A G BesnardBesnard, A G Researcher  
G B MenezesMenezes, G B Researcher  
T SecherSecher, T Researcher  
M S JabirJabir, M S Researcher  
S S AmaralAmaral, S S Researcher  
H BraunBraun, H Researcher  
R C P Lima-JuniorLima-Junior, R C P Researcher  
R A RibeiroRibeiro, R A Researcher  
F Q CunhaCunha, F Q Researcher  
G J GrahamGraham, G J Researcher  
M M TeixeiraTeixeira, M M Researcher  
R BeyaertBeyaert, R Researcher  
F Y LiewLiew, F Y Researcher  

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