MMP-9 and TIMPs profiles in sulfur mustard-exposed individuals with serious lung complications

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-01-03 DOI:10.1016/j.intimp.2024.113777

Faramarz Fallahi , Nayere Askari , Tahereh Jamali , Sara Parsapour , Hassan Ghasemi , Jalaledin Shams , Roya Yaraee , Zeinab Ghazanfari , Tooba Ghazanfari

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引用次数: 0

Abstract

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.

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硫芥菜暴露者严重肺部并发症的MMP-9和TIMPs谱

硫磺芥子气（SM）是两伊战争中使用的一种化学武器，会对健康造成严重威胁，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）的失调与各种炎症性肺部疾病有关。本研究比较了严重肺部并发症退伍军人血清和痰中MMPs和TIMPs的水平与对照组。采用ELISA夹心法采集血清和痰液进行分析。sm暴露组与对照组之间的差异进行统计学评估。sm暴露组血清中TIMP-4和MMP-9/TIMP-4水平分别显著低于对照组和高于对照组。在sm暴露个体中，如闭塞性细支气管炎（BO）、慢性支气管炎（CB）和哮喘，TIMP-4水平低于对照组，而CB组TIMP-2水平高于对照组。尽管这些患者中TIMP-2水平升高与COPD研究一致，但在COPD和哮喘相关的MMP-9和TIMP-4结果中，观察到其他因素的差异。根据严重程度评估这些因素的血清水平显示，与轻度-中度组相比，重度组的MMP-9/TIMP-4水平较低。暴露于SM的个体表现出明显的MMP和TIMP特征，与对照组相比，TIMP-4水平显著降低，MMP-9/TIMP-4比值显著升高。这些特征因不同的肺部状况而异，表明sm暴露个体中存在独特的疾病机制。这种独特的外形支持这种情况的分类为“芥菜肺”。需要进一步的研究来阐明这些靶向治疗干预的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.