title: Mutual amplification of HNF4α and IL-1R1 composes an inflammatory circuit in Helicobacter pylori associated gastric carcinogenesis.
abstract: Helicobacter pylori (Hp) is an environmental inducer of gastritis and gastric cancer (GC). The immune response to Hp and the associated changes in somatic gene expression are key determinants governing the transition from gastritis to GC. We show that hepatocyte nuclear factor 4α (HNF4α) is upregulated by Hp infection via NF-κB signaling and that its protein and mRNA levels are elevated in GC. HNF4α in turn stimulates expression of interleukin-1 receptor 1(IL-1R1), which amplifies the inflammatory response evoked by its ligand IL-1β. IL-1β/IL-1R1 activates NF-κB signaling, thereby increasing HNF4α expression and forming a feedback loop that sustains activation of the NF-κB pathway and drives the inflammation towards GC. Examination of clinical samples revealed that HNF4α and IL-1R1 levels increase with increasing severity of Hp-induced gastritis and reach their highest levels in GC. Co-expression of HNF4α and IL-1R1 was a crucial indicator of malignant transformation from gastritis to GC, and was associated with a poorer prognosis in GC patients. Disruption of the HNF4α/IL-1R1/IL-1β/NF-κB circuit during Hp infection maybe an effective means of preventing the associated GC.
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Lin
authors: L
authors: Ma
authors: Department of Biochemistry, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Jiping
authors: J
authors: Zeng
authors: Department of Nursing, Ningxia People's Hospital, Yinchuan 750021, Ningxia, PR China.
authors: Qing
authors: Q
authors: Guo
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Xiuming
authors: X
authors: Liang
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Li
authors: L
authors: Shen
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Shuyan
authors: S
authors: Li
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Yundong
authors: Y
authors: Sun
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Wenjuan
authors: W
authors: Li
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Shili
authors: S
authors: Liu
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Han
authors: H
authors: Yu
authors: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, Shandong, PR China.
authors: Chunyan
authors: C
authors: Chen
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
authors: Jihui
authors: J
authors: Jia
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007249:Inflammation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D014162:Transfection
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D016328:NF-kappa B; D053573:Receptors, Interleukin-1 Type I
keywords: HNF4α; Hp; IL-1R1; NF-κB; gastric carcinogenesis