Anti-inflammatory actions of probiotics through activating suppressor of cytokine signaling (SOCS) expression and signaling in Helicobacter pylori infection: a novel mechanism

Abstract

Background and aims: In spite of the International Agency for Research on Cancer's definition that Helicobacter pylori is the definite carcinogen of gastric cancer, the simple eradication of the bug is not enough to prevent resultant gastric cancer, and increasing microbial resistance further limits the eradication application. Therefore, probiotics, non-pathogenic microbial feed that can affect the host in a beneficial manner, could be an alternate way to enhance anti-inflammation against H. pylori. However, the mechanism of their anti-inflammatory actions is still unclear. In the current study, we hypothesized that suppressor of cytokine signaling (SOCS) signaling could be a feasible anti-inflammatory mechanism of probiotics against H. pylori infection.

Results: H. pylori infection or their lipopolysaccharide stimulation led to significant increased expressions of inflammatory mediators including tumor necrosis factor-alpha, interleukin-8, inducible nitric oxide synthase and cyclooxygenase-2 in AGS cells and pretreatment of Lactobacillus plantarum, Lactobacillus rhamnosis and Lactobacillus acidophilus significantly attenuated the expressions of these inflammatory mediators in accordance with the blocking action of nuclear factor-kappaB nuclear translocation. Probiotic administration increased expression of SOCS-2 and SOCS-3 and exerted the active SOCS signaling featured with earlier and higher expressions of SOCS-2 and SOCS-3. In contrast to weak inactivation of mitogen-activated protein kinases including p-38 and extracellular signal-regulated kinase 1/2, probiotic-induced SOCS expressions were mediated through either significant phosphorylation of signal transducers and activation of transcription (STAT)-1 and STAT-3 or simultaneous inhibition of Janus kinase (JAK)2 phosphorylation, which is known to signal SOCS-2/SOCS-3 negatively.

Conclusion: Anti-inflammatory signals of SOCS through STAT-1/STAT-3 activation and JAK2 inactivation might be a key anti-inflammatory mechanism of probiotics, setting probiotics as a non-microbial strategy to H. pylori infection.