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IL‐4 primes human endothelial cells for secondary responses to histamine
Author(s) -
Wierzbicki Tom,
Iqbal Shehzad M.,
Cuvelier Susan L.,
Awong Geneve,
Tibbles Lee Anne,
Patel Kamala D.
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1102571
Subject(s) - histamine , cytokine , biology , histamine h1 receptor , platelet activating factor , histamine h4 receptor , tumor necrosis factor alpha , umbilical vein , endocrinology , medicine , immunology , stimulation , histamine h2 receptor , receptor , antagonist , biochemistry , in vitro
Interleukin‐4 (IL‐4) is a multifunctional cytokine, which is involved in numerous disease states, including atopic asthma. IL‐4 not only induces direct responses in cells but can also prime for secondary responses to stimuli. Little is known about the priming effects of IL‐4 on endothelial cells; therefore, we chose to examine the ability of IL‐4 to prime endothelial cells for platelet‐activating factor (PAF) synthesis and prostaglandin E 2 (PGE 2 ) release. IL‐4 alone did not enhance PAF synthesis or PGE 2 release; however, pretreatment with IL‐4 primed for PAF synthesis and PGE 2 release in response to subsequent stimulation with histamine. In contrast, tumor necrosis factor α (TNF‐α), oncostatin M (OSM), and IL‐1β did not prime endothelial cells for PAF synthesis in response to histamine. The priming effects of IL‐4 occurred without any detectable changes in the requirement for signaling pathways upstream of PGE 2 release. IL‐4 treatment increased the expression of mRNA for histamine receptor 1 (HR1) and shifted the inhibition curve for pyrilamine, a specific HR1 antagonist. In addition, the dose‐response curve for histamine‐induced elevations in intracellular calcium was shifted following IL‐4 stimulation. Together, these data indicate that HR1 is up‐regulated in IL‐4‐stimulated human umbilical vein endothelial cells (HUVEC) and suggest that this up‐regulation may contribute to the enhanced responsiveness of IL‐4‐stimulated HUVEC to histamine.