Epithelial barrier cells (in skin, gut, and airway) are both active modulators and important targets of the inflammatory response, and some of these cellular events may be regulated at a molecular level by products of
phospholipid-
arachidonic acid metabolism. Accordingly, we have defined some of the characteristics of gene expression and
enzyme regulation for distinct members of the
PGH synthase and
lipoxygenase gene families in normal and inflamed epithelial tissues and in epithelial cells isolated from mucosal and epidermal tissue (Table 1). A unifying scheme for our findings includes the following enzymatic systems: (i) a
PGH synthase-1/PG
isomerase pathway responsible for constitutive generation of
prostaglandins (e.g.,
PGE2) and maintenance of physiologic epithelial function; (ii) a
PGH synthase-2/PG
isomerase and synthase pathway capable of producing additional
prostaglandins (e.g., excess
PGE2 and/or
PGF2 alpha and
PGD2) especially after stimulation by
growth factors and
cytokines; and (iii) a family of arachidonate 12- and 15-lipoxygenases that may serve to generate
hydroxy acids (e.g., 12- and 15-
HETE) as mediators of basal epithelial function and that (after overexpression and
oxidant activation) may also catalyze membrane peroxidation that contributes to epithelial damage during
inflammation. The regulatory mechanisms inherent in the control of this scheme provide a biochemical rationale for balancing constitutive and inducible oxygenation activities and maintaining epithelial barrier function.