Rationale and Objective Hormones, such as catecholamines, and pro-inflammatory cytokines were correlated with circadian rhythm, as well as acute coronary syndrome.Rev-erb α, a circadian controlling molecular, has been shown to regulate pro-inflammatory cytokines production in several cells. To study the effect of epinephrine on pro-inflammatory cytokines release from murine bone marrow derived mast cells(mBMMCs) and to investigate the effect of epinephrine on Mitogen-Activated Protein Kinase(MAPK), nuclear factor-κB(NF-κB) and circadian gene and the involved molecular mechanisms.Methods Bone marrow derived mast cells (mBMMCs) were cultured from femur and tibia of male C57BL/6 mouse (4-5 weeks old).Different doses of LPS and epinephrine were added into cultures.Then proteins involved inMAPK and NF-κB pathway were determined by western blot, IL-6 and TNF-α mRNA expression was assayed by real-time PCR and IL-6,TNF-α and MCP-1 secretion was determined by ELISA.PDTC (NF-κB inhibitor), PD98059 (ERK1/2 inhibitor) and SB203580(p38 inhibitor) were added into cultures, respectively.IL-6, TNF-α and MCP-1 were also determined by ELISA.Propranolol and atenolol were added into cultures to investigate the role of β2--adrenoreceptors played in the enhancing effect of epinephrine on pro-inflammatory cytokines production.Rev-erb α protein expression was determined by western blot.mBMMCs were challenged by GSK4112(Rev-erb α agonist) and SR8278(Rev-erb α antagonist) and siRNA were transfected into mBMMCs to suppress Rev-erb α expression.IL-6,TNF-α and MCP-1 were also determined by ELISA.Results Epinephrine enhanced pro-inflammatory cytokines release from LPSchallenged mBMMCs.And MAPK and NF-κB pathways were activation in epinephrine treated mast cells.The pro-inflammatory cytokines production was inhibited by inhibitors of MAPK and NF-κB pathways.Propranolol inhibited the enhancing effect of epinephrine on pro-inflammatory cytokines production from mBMMCs.But no such effect was observed in atenolol treated cells.Rev-erb α protein expression was increased in epinephrine treated mast cells.GSK4112 partially inhibited the enhancing effect of epinephrine, but accompanied by decreasing cell viability.However, SR8278, the antagonist of Rev-erb α down-regulated the production of IL-6 from LPS-challenged mBMMCs with an increasing cell viability.The enhancing effect of epinephrine on pro-inflammatory cytokines production was also inhibited by SR8278.Similar results were observed in mBMMCs transfected with anti-rev-erb αsiRNA.Conclusion Epinephrine could enhance pro-inflammatory cytokines production from LPS challenged mBMMCs through activated MAPK and NF-κB pathways.Activation of β2 adrenoreceptors and up-regulation of Rev-erb α expression was involved in the enhancing effect in mBMMCs.