IL-4 primes human endothelial cells for secondary responses to histamine.
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 alpha (TNF-alpha), oncostatin M (OSM), and IL-1beta 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.
Wierzbicki
Tom
T
Department of Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada.
Iqbal
Shehzad M
SM
Cuvelier
Susan L
SL
Awong
Geneve
G
Tibbles
Lee Anne
LA
Patel
Kamala D
KD
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D053683:Oncostatin M; D010120:Oxytocics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation
D007375:Interleukin-1; C508351:OSM protein, human; D010120:Oxytocics; D010455:Peptides; D010972:Platelet Activating Factor; D011968:Receptors, Histamine; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D015847:Interleukin-4; D006632:Histamine; D015232:Dinoprostone; D002118:Calcium