Allyl isothiocyanate ameliorates collagen-induced arthritis via mast cells and the pim1 pathway

ObjectivesThe present study explored whether allyl isothiocyanate from the traditional Chinese medicine mustard seed, ameliorated the arthritis by modulating immune cell responses, particularly by inhibiting mast cell activation and the Pim1 pathway.MethodsMicro-CT, hematoxylin and eosin staining, and flow cytometry were performed to evaluate pathological changes in collagen-induced arthritis mice. To investigate the mechanism underlying allyl isothiocyanate-mediated mast cells activation, degranulation, intracelluar calcium measurement, RNA sequencing, real-time polymerase chain reaction and western blotting were carried out.Key findingsAllyl isothiocyanate reduced the number of mast cells in the ankle joints of collagen-induced arthritis mice, and it inhibited the degranulation of mouse bone marrow-derived mast cells and RBL-2H3. RNA sequencing revealed that allyl isothiocyanate significantly inhibited Pim1 expression. Additionally, it inhibited the expression of Pim1, p-STAT5, p-AKT and c-myc in RBL-2H3 and RAW264.7 cells and the ankle joints of collagen-induced arthritis mice. Adoptive transfer of mouse bone marrow-derived mast cells early in collagen-induced arthritis exacerbated joint inflammation, which was similarly inhibited by allyl isothiocyanate.ConclusionThese findings support mast cell as a major cellular target of AITC in CIA and suggest that Pim1-related signaling contributes to AITC-mediated suppression of mast cell activation.