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Manzoor M Khan, Geetanjali Kharmate, Zhongfeng Liu, Role of H1 receptors in the regulation of IL-4 production (37.16), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S21, https://doi.org/10.4049/jimmunol.178.Supp.37.16
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Abstract
Histamine alters the Th1/Th2 cytokine balance towards the Th2 cytokine profile and consequently play a role in allergic disease and asthma. This study was designed to determine if the effects of histamine on Signal Transducer and Activator of Transcription(STAT)-6 were direct or mediated via release of IL-4 production.The splenocytes from IL-4 knockout C57Bl/6 mice were pretreated with antibody to IL-13 for 30 minutes followed by treatment with histamine. The cells were then stimulated with PMA + ininomycin for 6 hours under standard cell culture conditions. For the control experiments splenocytes from the wild type C57BL/6 mice were used. The cells were lyzed and the total basal and phosphorylated STAT6 were analyzed using the Western Blot Analysis. Furthermore, splenocytes from C57Bl/6 mice were pretreated with antibodies to IL-4 and IL-13 followed by treatment with histamine and PMA + ionomycin and Western blot analysis were performed to determine the phosphorylated Stat6 levels.In the control group histamine caused hyper-phosphorylation of Y641 tyrosine residues of STAT6. These effects were not observed when splenocytes from the IL-4 knockout mice were used or the wildtype splenocytes were pretreated with antibodies to IL-4 and IL-13. These observations suggest that histamine indirectly affected the heper-phosphorylation of STAT6 via its effects on the secretion of IL-4 and H1 receptors played a role in this process, since H1 receptor antagonists blocked these effects. The clinical significance of STAT6 hyper-phosphorylation in the exacerbation of asthma symptoms has not yet been determined.
