Histamine utilizes JAK–STAT pathway in regulating cytokine production

Abstract Histamine shifts TH1/TH2 cytokine balance from TH1 to TH2 cytokines. The phosphorylation of STAT factors and their translocation to nucleus are important steps in the regulation of TH1/TH2 cytokine balance. This study was designed to investigate the effects of histamine on Janus kinases–signal transducers and activators of transcription (JAK–STAT) pathway. The splenocytes were treated with histamine in the presence or absence of JAK–STAT inhibitor, tyrphostin, activated with IFNγ for 30 min, and phosphorylated STAT1 was detected by immunoblotting. We found that histamine up-regulated the phosphorylation of STAT1 and tyrphostin prevented this phosphorylation. We then studied the effects of tyrphostin on histamine-mediated inhibition of IFNγ production and histamine-mediated stimulation of IL-5 and IL-10 production. Tyrphostin dose-dependently reversed the effects of histamine on IFNγ, IL-5 and IL-10 production, as evident by ELISA. These observations suggest that histamine regulated JAK–STAT signal transduction, which is involved in cytokine secretion.