Histamine differentially regulates the production of Th1 and Th2 chemokines by keratinocytes through histamine H1 receptor

Regulation of the immune response and inflammation by histamine and histamine receptors

“…Human keratinocytes express H1R, and histamine suppressed CCL17 (a T H 2 chemokine) while enhancing CXCL10 (a T H 1 chemokine) secretion, suggesting that H1R might block T H 2 responses while enhancing T H 1 responses within the skin. 133 Histamine plays an important role in the immune response to infectious agents. Sedating first-generation H1R antihistamines and H2R blockers impair optimal innate immune responses in severe murine bacterial sepsis, suggesting that histamine signaling is required for appropriate defense against bacterial infection.…”

Introduction

“…In cultured keratinocytes, histamine through the activation of H 1 receptor inhibits CCL17 production by suppressing p38 MAP kinase and NF-κB activities. Histamine acts as a negative-feedback signal for existing Th2-dominant inflammation by suppressing CCL17 and enhancing CXCL10 production (Fujimoto et al, 2011). The effect of histamine acting through H2 receptor appears to be the opposite.…”

c-kit plays a critical role in induction of intravenous tolerance in experimental autoimmune encephalomyelitis

“…We also observed that H4 receptor expression decreased in both spleen and CNS after i.v. tolerance in the chronic phase of EAE, which may indicate its immunoregulatory role In mice, deletion of H1R results in suppression of IFN-γ and increased secretion of Th2 cytokines (IL-4 and IL-13), indicating an important regulatory mechanism in the control of inflammatory functions through the H1 pathway with a different intracellular signaling pathway (30–31). On the other hand, cells transmigrating to the H4R agonist, but not to H1R, were skewed toward CD4 cells expressing CD25 and intracellular FoxP3.…”

“…Mononuclear cells (MNCs) from pooled spinal cords were isolated as previously described (30). Cells were cultured overnight with MOG (10mg/ml) at 1×10 6 cells/ml concentration.…”

“…The specificity of CD117 staining was confirmed by the absence of staining in CNS tissue from W-sh mice (data not shown). Histochemical analysis of c-kit + cells was carried out as described before (30). Briefly, 5 μm thickness sections were de-waxed in xylene and rehydrated by decreasing concentrations of ethanol to distilled water.…”