Histamine utilizes JAK-STAT pathway in regulating cytokine production

Histamine shifts TH1/TH7 cytokine balance from TH1 to TH2 cytokines. The ph osphorylation of STAT factors and their translocation to nucleus are import ant steps in the regulation of TH1/TH2 cytokine balance. This study was des igned to investigate the effects of histamine on Janus kinases-signal trans ducers and activators of transcription (JAK-STAT) pathway. The splenocytes were treated with histamine in the presence or absence of JAK-STAT inhibito r, tyrphostin. activated with IFN gamma for 30 min, and phosphorylated STAT 1 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 IFN gamma production and histamine-mediated stimulation of IL-5 and IL-10 p roduction. Tyrphostin dose-dependently reversed the effects of histamine on IFN gamma, IL-5 and IL-10 production. as evident by ELISA. These observati ons suggest that histamine regulated JAK-STAT signal transduction, which is involved in cytokine secretion. (C) 2001 Elsevier Science B.V. All rights reserved.