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 : Wednesday, March 9, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
R GuabirabaGuabiraba, R Investigator  
AG BesnardBesnard, AG Researcher  
GB MenezesMenezes, GB Researcher  
T SecherSecher, T Researcher  
MS JabirJabir, MS Researcher  
SS AmaralAmaral, SS Researcher  
Harald BraunBraun, Harald Researcher  
R CP Lima-JuniorLima-Junior, R CP Researcher  
RA RibeiroRibeiro, RA Researcher  
FQ CunhaCunha, FQ Researcher  
FY LiewLiew, FY Researcher  

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