Initial MCs activation disappeared with decreased MrgprB2 expression after tacrolimus long-term treatment
To mimic tacrolimus clinical long-term use, 0.03% tacrolimus cream were applied on dorsal skin of mice twice per day. Strikingly, the earlier irritant manifestations (scratching and inflammatory cells infiltration) fade away with no skin IgE level change (Figure 6A, B and C). The levels of skin TNF-α, MCP-1, IL-8 and tryptase on day 7 and 11 are with no significant difference in the absence of additional C48/80 stimulation (Figure 6D). To assess the status of MC at this time, avidin staining was used, which showed no remarkable distinct in MCs infiltration and degranulation compared to control group (Figure 6E). Surprisingly, skin MrgprB2 expression was massively downregulated after 7-day and 11-day tacrolimus topical use in vitro (Figure 7F). Hence, we speculated that suppressed MrgprB2 expression may be involved in disappearance of initial MCs stimulation after longer tacrolimus treatment.