Fallahi Faramarz, Askari Nayere, Jamali Tahereh, Parsapour Sara, Ghasemi Hassan, Shams Jalaledin, Yaraee Roya, Ghazanfari Zeinab, Ghazanfari Tooba
Department of Cardiology, Faculty of Medicine, Shahed University, Tehran, Iran.
Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran; Immunoregulation Research Center, Shahed University, Tehran, Iran.
Int Immunopharmacol. 2025 Jan 3;145:113777. doi: 10.1016/j.intimp.2024.113777. Epub 2024 Dec 10.
Sulfur mustard (SM), a chemical weapon used in the Iraq-Iran war, can pose severe health risks, especially to the lungs. Dysregulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in various inflammatory lung diseases. This study compares the levels of MMPs and TIMPs in the serum and sputum of veterans with serious lung complications to a control group. Serum and sputum samples were collected and analyzed using the ELISA sandwich method. Differences between SM-exposed and control groups were assessed statistically. The serum levels of TIMP-4 and MMP-9/TIMP-4 were significantly lower and higher in the SM-exposed group respectively compared to the control group. In SM-exposed individuals resembling Bronchiolitis Obliterans (BO), Chronic Bronchitis (CB), and Asthma, TIMP-4 levels were lower than controls, while TIMP-2 levels were higher in those with CB. Although the increased TIMP-2 levels in these patients align with COPD studies, differences were observed in other factors with COPD and asthma-related MMP-9 and TIMP-4 findings. Assessment of serum levels of these factors based on severity reveals lower MMP-9/TIMP-4 levels in the severe group compared to the mild-moderate group. Individuals exposed to SM exhibit distinct MMP and TIMP profiles, with significantly lower TIMP-4 levels and higher MMP-9/TIMP-4 ratios, compared to controls. These profiles vary across different lung conditions, indicating a unique disease mechanism in SM-exposed individuals. This distinctive profile supports the classification of this condition as 'Mustard Lung.' Further research is needed to elucidate these mechanisms for targeted therapeutic interventions.
硫芥气(SM)是一种在两伊战争中使用的化学武器,会带来严重的健康风险,尤其是对肺部。基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)的失调与多种炎症性肺部疾病有关。本研究比较了患有严重肺部并发症的退伍军人血清和痰液中MMPs和TIMPs的水平与对照组的差异。收集血清和痰液样本并采用酶联免疫吸附测定夹心方法进行分析。对硫芥气暴露组和对照组之间的差异进行统计学评估。与对照组相比,硫芥气暴露组血清中TIMP-4水平显著降低,而MMP-9/TIMP-4水平显著升高。在患有闭塞性细支气管炎(BO)、慢性支气管炎(CB)和哮喘的硫芥气暴露个体中,TIMP-4水平低于对照组,而CB患者的TIMP-2水平较高。尽管这些患者中TIMP-2水平升高与慢性阻塞性肺疾病(COPD)的研究结果一致,但在其他与COPD和哮喘相关的MMP-9和TIMP-4研究因素中观察到了差异。根据严重程度评估这些因素的血清水平,结果显示重度组的MMP-9/TIMP-4水平低于轻度-中度组。与对照组相比,暴露于硫芥气的个体表现出独特的MMP和TIMP谱,TIMP-4水平显著降低,MMP-9/TIMP-4比值升高。这些谱在不同的肺部疾病中有所不同,表明硫芥气暴露个体存在独特的疾病机制。这种独特的谱支持将这种疾病归类为“芥子气肺”。需要进一步研究以阐明这些机制,以便进行有针对性的治疗干预。