Role Of IL-11/STAT3 Signal Pathway In Human Chronic Atrophic Gastritis

Objective: To explore the role of IL-11/STAT3 signal pathway in chronic atrophic gastritis(CAG),the expressions of IL-11 and its downstream products STAT3, p-STAT3 protein in gastric mucosa of patients with chronic superficial gastritis(CSG), chronic atrophic gastritis(CAG) and gastric cancer(GC) as well as the serum IL-11 level in the serum of patients in each group will be measured.Methods:90 patients with CSG, CAG and GC(30 in each group) were selected according to the endoscopic examination and confirmed by pathological diagnosis Then the gastric mucosa specimen and serum samples of these patients in each group were collected. Firstly, the expressions of IL-11, STAT3 and phosphorylated STAT3(p-STAT3) proteins were detected by immunohistochemistry(IHC). Then the expressions of STAT3 and p-STAT3 were examined by western blot analysis. The IL-11 mRNA was quantified in real-time polymerase chain reaction(RT-PCR). In addition, the serum levels of IL-11 protein were measured by enzyme-linked immunosorbent assay(ELISA).Results(1) Among 30 cases of the CAG patients, 18 cases(60%) showed positive staining for the IL-11, while the positive rate of IL-11 in carcinoma cells was 83.3%(25/30) using IHC staining. Both of them were markedly higher than that of CSG(33.3%,10/30). Moreover, the positive rate of GC was significantly higher than that of CAG(p<0.05);The positive rate of CAG(80%,24/30) and GC(83.3%,25/30) were significantly higher than that in CSG(53.3%,16/30)(p<0.05).Compared with the CSG(36.7%,11/30), the positive rates of p-STAT3 protein expression in the CAG(63.3%,19/30) and GC(86.7%,26/30) were also significantly higher.(2)The expression of STAT3 protein in GC was similar to that in CAG, which were both significantly higher than that in CSG. As expected, the p-STAT3 protein expressions in CAG and GC were significantly higher than that in CSG in western blot analysis. Furthermore, the activation of STAT3 was markedly higher in GC tissues than that in CAG(p<0.01).(3)However, no statistically significant difference was found between the IL-11 mRNA in CSG and CAG though IL-11 mRNA in GC group was statistically higher than both of them.(4)Exhilaratingly, serum IL-11 levels were gradually increased from CSG(72.91±9.89 pg/ml) to CAG(166.00±15.19 pg/ml) to GC(216.34±22.57 pg/ml), along with the severity of gastric disease. These results were coincided with the results of IHC.Conclusion The expressions of IL-11 and p-STAT3 protein are significantly upregulated in human CAG and gastric adenocarcinoma in comparison with that in CSG. Furthermore, there are significant differences between the expressions of IL-11 and p-STAT3 in CAG and GC. It suggests that IL-11-STAT3 signal pathway may play a critical role in human CAG. It may provide new targets for the prevention and treatment of CAG and GC and has important potential clinical application.