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. © 2001 Elsevier Science B.V.