Department of Otolaryngology-Head and Neck Surgery, University of Missouri, Columbia, Missouri.
Department of Otolaryngology, Department of Surgery, The University of Utah, Salt Lake City, Utah.
J Histochem Cytochem. 2021 Aug;69(8):523-534. doi: 10.1369/00221554211031678.
Radiation therapy-mediated salivary gland destruction is characterized by increased inflammatory cell infiltration and fibrosis, both of which ultimately lead to salivary gland hypofunction. However, current treatments (e.g., artificial saliva and sialagogues) only promote temporary relief of symptoms. As such, developing alternative measures against radiation damage is critical for restoring salivary gland structure and function. One promising option for managing radiation therapy-mediated damage in salivary glands is by activation of specialized proresolving lipid mediator receptors due to their demonstrated role in resolution of inflammation and fibrosis in many tissues. Nonetheless, little is known about the presence and function of these receptors in healthy and/or irradiated salivary glands. Therefore, the goal of this study was to detect whether these specialized proresolving lipid mediator receptors are expressed in healthy salivary glands and, if so, if they are maintained after radiation therapy-mediated damage. Our results indicate that specialized proresolving lipid mediator receptors are heterogeneously expressed in inflammatory as well as in acinar and ductal cells within human submandibular glands and that their expression persists after radiation therapy. These findings suggest that epithelial cells as well as resident immune cells represent potential targets for modulation of resolution of inflammation and fibrosis in irradiated salivary glands.
放射治疗介导的唾液腺破坏的特征是炎症细胞浸润和纤维化增加,两者最终导致唾液腺功能低下。然而,目前的治疗方法(如人工唾液和唾液刺激剂)只能暂时缓解症状。因此,开发针对辐射损伤的替代措施对于恢复唾液腺的结构和功能至关重要。一种有前途的管理唾液腺放射治疗介导损伤的方法是通过激活专门的促解决脂质介质受体,因为它们在许多组织中炎症和纤维化的解决中发挥了作用。尽管如此,对于这些受体在健康和/或受照射的唾液腺中的存在和功能知之甚少。因此,本研究的目的是检测这些专门的促解决脂质介质受体是否在健康的唾液腺中表达,如果是,它们是否在放射治疗介导的损伤后仍然存在。我们的结果表明,专门的促解决脂质介质受体在人颌下腺的炎症细胞以及腺泡和导管细胞中呈异质性表达,并且它们的表达在放射治疗后仍然存在。这些发现表明上皮细胞以及驻留免疫细胞代表了调节受照射唾液腺中炎症和纤维化解决的潜在靶点。