Anti-inflammatory Mechanism of Astragaloside IV in the Recurrence of Asthma: Critical Role of Memory T Cells and OX40/OX40L Signaling Pathway

Abstract

Background: Astragaloside IV (AST) has been confirmed to have antiasthmatic effects by our research. However, the underline mechanism is unclear. Memory CD4(+) T cells play an important role in the recurrence of asthma, the study try to explore the immunoregulatory effect from memory T cells.Methods and Results: Flow cytometry was used to determine the counts of memory T cells in blood and spleen; Pulmonary tests, inflammatory cytokines in blood and inflammatory cells in bronchoalveolar lavage fluid were measured to evaluate the inflammatory response. The central memory CD4(+) T cells (TCM) were isolated and adoptive transferred into nude mice via tail intravenous, after OVA challenge 3 days, the lung inflammation was measured. Results shown the TCM phenotype was increased in spleen but the TEM was decreased. On the contrary, the number of actived TEM was increased, but the number of inactived TCM was decreased in asthmatic mice circulation; AST treatment significantly decreased TCM in the spleen and T effector phenotypes in blood. OX40/OX40L pathway expression were significantly increased in asthma spleen, AST pretreatment inhibited the OX40 signal pathway expression. Additionally, the adoptive transferred TCMs from AST treatment mice had relieved inflammation compared with asthma group.Conclusions: This study indicates that AST can ameliorate asthma inflammation by decreaseing the ration of TEM/TCM in blood. The anti-inflammatory mechanism maybe involved in the OX40/OX40L pathway.