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Liu et al. Th17 activation by H. pylori and triglyceride

uninfected individuals did so [Figure 4B]. has been shown to be beneficial in preventing
GC development. [31,32] Obesity and diabetes have
RORγt is the most important transcription factor for become a great problem in modern societies, which
the differentiation and activation of Th17 cells. [30] profoundly increase the frequencies of malignant
We thus analyzed RORγt expression in H. pylori- neoplasms, including GC. [21,33,34] Although H. pylori
associated GC and explored its potential role in tumor infection and metabolic disorders can independently
progression. We found that an overall 6-fold increase promote tumor progression, there are considerable
of RORγt in H. pylori-infected vs. uninfected GC evidences showing that they can also exert a
[Figure 4C], and that H. pylori-associated expression synergistic effect on tumorigenesis. [19] However, the
of RORγt and IL-17A were positively correlated molecular mechanisms behind this synergy remain
[Figure 4D]. In the absence of H. pylori infection, elusive. We previously reported that H. felis-induced
the levels of RORγt were not different between early GC in obese mice can be influenced by the gastric
and advanced tumors [Figure 4E and F]. In contrast, homing and activation of Th17 cells, which trigger a
RORγt expression was further enhanced in H. pylori- series of inflammatory responses in both stomach
associated tumor progression, with higher expression and adipose tissues through releasing IL-17A. [19]
in larger tumors (> 4 cm) [Figure 4E] and those with Our current results further the concept that chronic
more metastatic capability (T3/T4 stages) [Figure 4F]. H. pylori infection and aberrant lipid metabolism can
interact to activate Th17 responses and facilitate GC.
DISCUSSION
We demonstrate that H. pylori infection is associated
It has been long recognized that unresolved with striking elevation of IL-17A content in GC
inflammation induced by H. pylori will favor [Figure 1A]. The expression of IL-17A is also
gastric carcinogenesis. Eradication of H. pylori increased in the patients with abnormal high plasma

Figure 3: H. pylori induced GM-CSF and CXCL1 expression. (A and C)The quantitative assays of GM-CSF (A) and CXCL1 (C) were
performed by RT-qPCR. ***P < 0.001, HP (+) vs. HP (-); (B and D) the correlation of GM-CSF (B) and CXCL1 (D) with IL-17A expression
was analyzed. H. pylori: Helicobacter pylori; RT-qPCR: reverse transcription quantitative polymerase chain reaction; IL: interleukin; CXCL1:
chemokine (C-X-C motif) ligand 1; GM-CSF: granulocyte-macrophage colony-stimulating factor
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ August 29, 2017 173