Clapp Carmen, Ortiz Georgina, García-Rodrigo Jose F, Ledesma-Colunga María G, Martínez-Díaz Oscar F, Adán Norma, Martínez de la Escalera Gonzalo
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, Mexico.
Front Endocrinol (Lausanne). 2022 Jun 2;13:905756. doi: 10.3389/fendo.2022.905756. eCollection 2022.
The term inflammatory arthritis defines a family of diseases, including rheumatoid arthritis (RA), caused by an overactive immune system, and influenced by host aspects including sex, reproductive state, and stress. Prolactin (PRL) is a sexually dimorphic, reproductive, stress-related hormone long-linked to RA under the general assumption that it aggravates the disease. However, this conclusion remains controversial since PRL has both negative and positive outcomes in RA that may depend on the hormone circulating levels, synthesis by joint tissues, and complex interactions at the inflammatory milieu. The inflamed joint is rich in matrix metalloproteases that cleave PRL to vasoinhibin, a PRL fragment with proinflammatory effects and the ability to inhibit the hyperpermeability and growth of blood vessels. This review addresses this field with the idea that explanatory mechanisms lie within the PRL/vasoinhibin axis, an integrative framework influencing not only the levels of systemic and local PRL, but also the proteolytic conversion of PRL to vasoinhibin, as vasoinhibin itself has dual actions on joint inflammation. In this review, we discuss recent findings from mouse models suggesting the upregulation of endogenous vasoinhibin by the pro-inflammatory environment and showing dichotomous actions and signaling mechanisms of PRL and vasoinhibin on joint inflammation that are cell-specific and context-dependent. We hypothesize that these opposing actions work together to balance the inflammatory response and provide new insights for understanding the pathophysiology of RA and the development of new treatments.
炎症性关节炎这一术语定义了一类疾病，包括类风湿性关节炎（RA），它由过度活跃的免疫系统引起，并受宿主因素影响，包括性别、生殖状态和压力。催乳素（PRL）是一种具有性别差异、与生殖及压力相关的激素，长期以来在普遍认为它会加重疾病的情况下与类风湿性关节炎相关联。然而，这一结论仍存在争议，因为催乳素在类风湿性关节炎中既有负面作用也有正面作用，这可能取决于激素的循环水平、关节组织的合成以及炎症环境中的复杂相互作用。发炎的关节富含基质金属蛋白酶，这些酶将催乳素切割成血管抑制素，血管抑制素是一种具有促炎作用且能抑制血管高通透性和生长的催乳素片段。本综述探讨这一领域，认为解释机制存在于催乳素/血管抑制素轴内，这是一个综合框架，不仅影响全身和局部催乳素的水平，还影响催乳素向血管抑制素的蛋白水解转化，因为血管抑制素本身对关节炎症具有双重作用。在本综述中，我们讨论了来自小鼠模型的最新发现，这些发现表明促炎环境上调内源性血管抑制素，并显示了催乳素和血管抑制素对关节炎症的二分作用和信号传导机制，这些作用具有细胞特异性且依赖于环境。我们假设这些相反的作用共同平衡炎症反应，并为理解类风湿性关节炎的病理生理学和开发新疗法提供新的见解。
