Histamine utilizes JAK-STAT pathway in regulating cytokine production.
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 IFNgamma for 30 min, and phosphorylated STAT1 was detected by immunoblotting. We found that histamine up-regulated the phosphorylation of STATI and tyrphostin prevented this phosphorylation. We then studied the effects of tyrphostin on histamine-mediated inhibition of IFNgamma production and histamine-mediated stimulation of IL-5 and IL-10 production. Tyrphostin dose-dependently reversed the effects of histamine on IFNgamma, 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.
Osna
N
N
Department of Pharmaceutical and Administrative Sciences, Creighton University, Omaha, NE 68178, USA.
Elliott
K
K
Chaika
O
O
Patterson
E
E
Lewis
R E
RE
Khan
M M
MM
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D053614:Janus Kinase 2; D051379:Mice; D008806:Mice, Inbred AKR; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D015848:Interleukin-5; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; D006632:Histamine; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2