title: Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis.
abstract: OBJECTIVE
  To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis.
  
  
  METHODS
  Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p-STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting.
  
  
  RESULTS
  Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.
  
  
  CONCLUSIONS
  IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Lian-Zhen
authors.initials: LZ
authors.lastname: Yu
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Wang
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Yang
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Yuan
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Xu
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D010766:Phosphorylation; D018123:Receptors, Interleukin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013997:Time Factors; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D053759:Interleukin-23; D007378:Interleukins; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C515500:IL23R protein, human; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C528688:interleukin-23 receptor, mouse
keywords: Interleukin-22; Interleukin-22R1; STAT3; Ulcerative colitis; Ulcerative colitis-related carcinogenesis