Mantha Kameswara Bharadwaj, Gajendran Mohan Kumar
University of Minnesota, Twin Cities, Minneapolis, MN, United States.
School of Science and Engineering, University of Missouri-Kansas City, Kansas City, MO, United States.
Front Med (Lausanne). 2025 Jul 17;12:1538368. doi: 10.3389/fmed.2025.1538368. eCollection 2025.
Recent studies emphasize the role of immune dysregulation and inflammation in endometriosis (ES). While hormonal therapy remains the primary treatment, emerging research is exploring synergistic approaches that target inflammation. In this study, we investigate the potential of H1-antihistamines (H1-As) in ES management from a gene-regulation viewpoint.
We perform differential gene expression analysis on two gene-sequencing datasets from ES patients, with a primar focus on inflammatory signaling [nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF), and cytokine-cytokine receptor] and histamine synthesis and metabolism (HSM) pathways, considering disease severity and hormonal therapy usage.
RESULTS & DISCUSSION: Consistent with the literature, our findings highlight the dysregulation of several genes involved in pro-inflammatory pathways, including interleukins (ILs), cyclooxygenase-2 (COX-2), chemokine ligands, cellular adhesionmolecules, and neuroangiogenesis. We also note dysregulation of genes in the HSM pathway, indicative of a microenvironment that favors histamine availability and inflammatory persistence through enhanced histamine synthesis and reduced breakdown, as well as a reduced potential to clear reactive aldehyde species. We also find that hormonal therapy minimally affects the dysregulation of the majority of pro-inflammatory and histaminic pathway genes, and their amplified dysregulation is noted in early stage disease. By placing our findings in the context of existing evidence on histamine-mediated modulation of inflammatory pathways via the H1 histamine receptor (HRH1), we present a comprehensive discussion on the potential therapeutic value of H1-As in ES management due to their anti-inflammatory and mast-cellstabilizing properties.
近期研究强调了免疫失调和炎症在子宫内膜异位症（ES）中的作用。虽然激素疗法仍然是主要治疗方法，但新兴研究正在探索针对炎症的协同方法。在本研究中，我们从基因调控的角度研究了H1抗组胺药（H1-As）在ES治疗中的潜力。
我们对来自ES患者的两个基因测序数据集进行差异基因表达分析，主要关注炎症信号通路[核因子-κB（NF-κB）、肿瘤坏死因子（TNF）和细胞因子-细胞因子受体]以及组胺合成和代谢（HSM）途径，同时考虑疾病严重程度和激素疗法的使用情况。
与文献一致，我们的研究结果突出了参与促炎途径的几个基因的失调，包括白细胞介素（ILs）、环氧化酶-2（COX-2）、趋化因子配体、细胞粘附分子和神经血管生成。我们还注意到HSM途径中的基因失调，这表明通过增强组胺合成和减少分解，有利于组胺可用性和炎症持续存在的微环境，以及清除反应性醛类物质的潜力降低。我们还发现，激素疗法对大多数促炎和组胺途径基因的失调影响最小，并且在疾病早期阶段观察到它们的失调加剧。通过将我们的研究结果置于现有证据的背景下，即组胺通过H1组胺受体（HRH1）介导炎症途径的调节，我们对H1-As由于其抗炎和稳定肥大细胞的特性在ES治疗中的潜在治疗价值进行了全面讨论。
