Wound Inflammation in Diabetic ob/ob Mice Functional Coupling of Prostaglandin Biosynthesis to Cyclooxygenase-1 Activity in Diabetes-Impaired Wound Healing

This study focused on the regulation of prostaglandin (PG) production in diabetes-impaired wound tissue. Cyclooxygenase (COX)- 1 and-2 expression and activity were severely dysregulated in chronic wounds of dia-betic ob/ob mice. Those wounds were characterized by a reduced expression of COX-1 and the presence of strongly elevated levels of COX-2 when compared with conditions observed in healthy animals. Resolution of the diabetic and impaired wound-healing phenotype by systemic administration of leptin into ob/ob mice in-creased COX-1 expression in wound margin keratino-cytes and decreased COX-2 expression in inner wound areas to levels found in wild-type animals. Notably, improved wound healing was characterized by a marked increase in PGE2/PGD2 biosynthesis that colocalize