DIFFERENTIAL EXPRESSION OF VASCULAR CELL-ADHESION MOLECULE MESSENGER-RNA AND PROTEIN IN NASAL-MUCOSA IN RESPONSE TO IL-1 OR TUMOR-NECROSIS-FACTOR

IL-1 and tumor necrosis factor (TNF) are cytokines that share many ove rlapping functions, including induction of expression of the vascular cell adhesion molecule (VCAM) by endothelial cells. However, because m ost studies of cytokine induction of adhesion molecules have used huma n umbilical vein endothelial cells (HUVECs) and not microvascular endo thelial cells, the functional significance of such observations to sit es of allergic inflammation, such as the nasal mucosa, are at present unknown. We have therefore used nasal mucosa to compare the functional response of these microvascular endothelial cells with HUVECs. HUVECs or nasal mucosal explants were stimulated in vitro with varying conce ntration of IL-1 or TNF for 0 to 48 hours, and VCAM mRNA and protein e xpression were determined by means of immunostaining and in situ hybri dization. TNF and IL-1 were equivalent in their ability to induce VCAM mRNA and protein expression by HUVECs. In contrast, TNF was significa ntly more potent than IL-1 inducing VCAM mRNA and protein expression b y nasal mucosal microvascular endothelial cells. The recovery of signi ficant amount of IL-1 after incubation of recombinant IL-1 with nasal mucosa, as well as the ability of IL-1 to induce intercellular adhesio n molecule expression by nasal mucosa, suggests that neither degradati on of IL-1 nor downregulation of IL-1 receptors in nasal mucosa is lik ely to explain the inability of IL-1 to induce VCAM expression by nasa l mucosa. These studies suggest that microvascular endothelial cells i n the nasal mucosa differ functionally from HUVECs and that TNF may be more important than IL-1 in induction of VCAM expression in the nasal mucosa.