title: Neutrophil infiltration favors colitis-associated tumorigenesis by activating the interleukin-1 (IL-1)/IL-6 axis.
abstract: Neutrophil infiltration is a key event in chronic intestinal inflammation and associated colorectal cancer, but how these cells support cancer development is poorly understood. In this study, using a mouse model of colitis-associated cancer (CAC), we have demonstrated that infiltrated neutrophils produce large amounts of interleukin-1 (IL)-1β that is critical for the development of CAC. Depletion of neutrophil or blockade of IL-1β activity significantly reduced mucosal damage and tumor formation. This protumorigenic function of IL-1β was mainly attributed to increased IL-6 secretion by intestine-resident mononuclear phagocytes (MPs). Furthermore, commensal flora-derived lipopolysaccharide (LPS) was identified to trigger IL-1β expression in neutrophils. Importantly, accumulation of IL-1β-expressing neutrophils was seen in lesions of patients suffering from ulceratic CAC and these infiltrated neutrophils induced IL-6 production by intestinal MPs in an IL-1β-dependent manner. Overall, these findings reveal that in CAC milieu, infiltrating neutrophils secrete IL-1β that promotes tumorigenesis by inducing IL-6 production by intestinal MPs.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China [2] Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha, People's Republic of China.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: G-C
authors.initials: GC
authors.lastname: Han
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: R-X
authors.initials: RX
authors.lastname: Wang
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: C-M
authors.initials: CM
authors.lastname: Hou
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: R-F
authors.initials: RF
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, General Hospital of the PLA, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: B-F
authors.initials: BF
authors.lastname: Shen
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: G-J
authors.initials: GJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000150:complications* / Q000276:immunology*; D003110:Colonic Neoplasms / Q000209:etiology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D020556:Neutrophil Infiltration / Q000276:immunology*; D016133:Polymerase Chain Reaction
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6