Crocin’s effect on phenotype switching of J۷۷۴A.۱ macrophages depends on their polarization state during exposure

Objective(s): Macrophages exhibit versatile phenotypes, with M۱ macrophages releasing inflammatory cytokines and possessing microbicidal activities, while M۲ macrophages release anti-inflammatory cytokines and contribute to tissue repair. The M۱/M۲ imbalance plays a significant role in various pathological processes. Crocin, known for its antioxidant properties and ability to eliminate free radicals, has been investigated for its potential anti-inflammatory effects. We examined the effect of the primary activation state of macrophages on their phenotype switching when exposed to crocin.Materials and Methods: The crocin impact on macrophage viability was evaluated by MTT. TNF-α, IL-۶, and IL-۱۰ secretion, as well as Nos۲/Arg۱ ratio, were measured in cells treated with crocin or LPS+IFN-γ (M۱ inducers), in cells concurrently treated with crocin and LPS+IFN-γ or in cells pretreated with crocin before M۱ induction.Results: Crocin did not show any toxicity at the concentration of ۵۰۰ µM or lower. When uncommitted macrophages were exposed to crocin (۲۵-۱۰۰ µM), it elevated certain M۱ activity indicators, including Nos۲/Arg۱ ratio and TNF-α secretion, but not IL-۶. Crocin in concurrent treatment with LPS+IFN-γ prevented the increase in M۱ indicators, Nos۲/Arg۱ ratio, and TNF-α secretion. However, pretreatment of cells with crocin before the addition of LPS+IFN-γ did not reverse M۱ induction in macrophages; instead, it further increased the Nos۲/Arg۱ ratio and TNF-α secretion. IL-۱۰ was not detectable in any of the experimental groups.Conclusion: It appears that the modulatory effects of crocin on macrophage M۱/M۲ phenotype switching partly depend on the presence or absence of inflammatory mediators and, accordingly, the initial state of macrophage commitment.

کلیدواژه ها:

Arg۱ ، Crocin ، Inflammation ، Macrophage ، Nos۲ ، Saffron