前列腺素是参与生理过程的脂质介质,如血管收缩或扩张,还有病理生理过程,包括炎症,疼痛和发烧。它们由生物体中几乎所有细胞类型通过前列腺素内过氧化物合酶/环氧合酶的活化而产生。诱导型前列腺素内过氧化物合酶2/环氧合酶2(PTGS2/COX2)在与炎症信号相关的病理中起重要作用。PTGS2/COX2表达和活化的主要产物是前列腺素E2(PGE2),促进了各种各样的组织特异性效应,待环境投入。PGE2的主要来源之一是浸润的炎症细胞-该分子的产生在受损组织中急剧增加。免疫浸润是1型糖尿病的标志,导致自身免疫介导的胰腺β细胞破坏的多因素疾病。已经报道了PTGS2/COX2-PGE2信号级联在糖尿病性条件下的胰岛细胞中的有争议的作用,同时分配PGE2,炎症的原因和后果。在这里,我们以组织特异性方式回顾了该分子途径的主要作用,特别强调β细胞质量保护/破坏及其在T1DM预防或发展中的潜在作用。我们还讨论了针对该途径的未来治疗策略。
Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which include inflammation, pain and fever. They are produced by almost all cell types in the organism by activation of Prostaglandin endoperoxide synthases/Cyclooxygenases. The inducible Prostaglandin Endoperoxide Synthase 2/Cyclooxygenase 2 (PTGS2/COX2) plays an important role in pathologies associated with inflammatory signaling. The main product derived from PTGS2/COX2 expression and activation is Prostaglandin E2 (PGE2), which promotes a wide variety of tissue-specific effects, pending environmental inputs. One of the major sources of PGE2 are infiltrating inflammatory cells - the production of this molecule increases drastically in damaged tissues. Immune infiltration is a hallmark of type 1 diabetes mellitus, a multifactorial disease that leads to autoimmune-mediated pancreatic beta cell destruction. Controversial effects for the PTGS2/COX2-PGE2 signaling cascade in pancreatic islet cells subjected to diabetogenic conditions have been reported, allocating PGE2 as both, cause and consequence of inflammation. Herein, we review the main effects of this molecular pathway in a tissue-specific manner, with a special emphasis on beta cell mass protection/destruction and its potential role in the prevention or development of T1DM. We also discuss strategies to target this pathway for future therapies.