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Prostaglandin H Synthase and Lipoxygenase Gene Families in the Epithelial Cell Barrier a
Author(s) -
HOLTZMAN MICHAEL J.,
ZHANG VIVIAN,
HUSSAIN HAMEDA,
ROSWIT WILLIAM T.,
WILSON JOHN D.
Publication year - 1994
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1994.tb52724.x
Subject(s) - atp synthase , arachidonic acid , barrier function , prostaglandin d2 , enzyme , microbiology and biotechnology , chemistry , biochemistry , biology , prostaglandin
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.