The Effects of Probiotics and Pparγ on the Murine Model of Allergic Asthma

Probiotics are normal inhabitants in the gastrointestinal tracts of man and are widely considered to exert a number of beneficial roles including immunomodulation, interference with enteric pathogens, and maintenance of a healthy intestinal microflora. In recent years, studies of probiotics have also confirmed their extra-intestinal effects, particularly for the prevention of allergic diseases. However, the anti-allergy mechanism of probiotics is still unclear. In the first part of this study, we found that continuous feeding of Lactobacillus gasseri (L. gasseri) 10⁷ CFU/200 ml or 10⁹ CFU/200 ml for 4 weeks in Der p-sensitized and challenged mice could prevent allergen-induced airway inflammation. There were also significant changes of airway hypersensitivity, T_H1 and T_H2 cytokine patterns, lymphocyte proliferations and immunoglobulin production between L. gasseri -treated and non-treated mice. In the second part of study, we applied microarray analysis of the lung draining lymph nodes and mesenteric lymph node of mice to detect genes expression signal pathways and genetic profiling of immunological tolerance induced by L. gasseri that plays an essential role of in the prevention and therapeutic effects on allergic asthma. We found that there was significantly decrease of inflammatory and chemokines genes expression and increased of carbohydrate and lipid metabolism genes expression in the L. gasseri-treated mice as compared to non-treated sensitized and challenged mice. Thirdly, we have picked up one candidate targeted gene, PPARγ (peroxisome proliferator-activated receptor γ), to study the beneficial effect of probiotics on the allergic induced airway inflammation. Previously, it has been reported that PPARγ is a member of the nuclear hormone receptor family that not only is prominently involved in adipogenesis and metabolic regulation but also exerts pleiotropic anti-inflammatory effects in the lung, we hypothesized that PPARγ may play an important role in allergen-induced airway inflammation. The allergen-sensitized effect on murine model of asthma was applied in PPARγ P456L mutant mice by evaluating AHR, total numbers of inflammatory cells and cytokines secretion in bronchoalveolar fluid (BALF), and lung inflammation after mite allergen sensitization and challenge. Moreover, probiotics treatments PPARγ P456L mutant mice and wide type mice were administrated in allergen-sensitized mice. In summary, our results showed that PPARγ play important role in the inhibitory effect of allergen-induced airway inflammation in mice. And the anti-allergic effect on L. gasseri  may through activation of PPARγ to alleviate airway inflammation in allergen-sensitized murine model of asthma.