Dynamics of matrix metalloproteinases and their tissue inhibitors in patients with herpesvirus and papillomavirus infection

T. Nevezhkina, M. Chernikova, E. Markelova, M. S. Tulupova, Anna V. Kostyshko, L. Fedyanina, N. Markova
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Abstract

Sexually transmitted infections are of great importance for the proper reproductive function in women. Chronic inflammatory process leads to reproductive disorders. A special role in the chronic inflammatory process is attributed to papillomavirus (PVI) and herpetic infection. MMP-2 and MMP-9 enzymes cleave type 4 collagen which makes the scaffold of basement membranes and contributes to the separation of endothelial cells from the membranes, followed by their further migration and direct participation in angiogenesis thus affecting the growth of tumors, in particular cervical cancer. Tissue inhibitors of matrix metalloproteinases are known to limit the collagen breakdown. However, the imbalance of MMP and TIMP is accompanied by accumulation of extracellular matrix and increased risk for reproductive disorders. The aim of our study was to evaluate the dynamics of acute-phase proteins affecting the state of intercellular matrix (MMP-2, MMP-9 and MMP tissue inhibitors (type 1, 2) in blood serum of patients with PVI or coinfection of PVI and HSV before and after therapy with drugs exhibiting antiviral and immunomodulatory effects, i.e., a synthetic compound (Inosine pranobex) and vegetable substance (Solanum tuberosum). We have examined 141 patients with papillomavirus and herpetic infections treated with Inosine pranobex and Solanum tuderosum. Determination of MMP-2, MMP-9 and TIMP-1, TIMP-2 levels of in blood serum was carried out using specific reagents from RD Diagnostics Inc. (USA). The drug therapy with active substances of Inosine pranobex and Solanum tuberosum was associated with positive dynamics of the level of MMP-2, MMP-9 and tissue inhibitors of types 1 and 2 in all groups under studies. However, Inosine Pranobex exerts more pronounced changes, especially in subgroups with viral coinfections.
疱疹病毒和乳头瘤病毒感染患者基质金属蛋白酶及其组织抑制剂的动态变化
性传播疾病对妇女的正常生殖功能至关重要。慢性炎症过程导致生殖障碍。在慢性炎症过程中的特殊作用归因于乳头瘤病毒(PVI)和疱疹感染。MMP-2和MMP-9酶裂解4型胶原蛋白,使基底膜形成支架,使内皮细胞从基底膜分离,并进一步迁移,直接参与血管生成,从而影响肿瘤,特别是宫颈癌的生长。已知基质金属蛋白酶的组织抑制剂可以限制胶原蛋白的分解。然而,MMP和TIMP的失衡伴随着细胞外基质的积累和生殖障碍的风险增加。我们的研究目的是评估急性期蛋白对PVI或PVI和HSV合并感染患者血清中细胞间基质状态的影响(MMP-2, MMP-9和MMP组织抑制剂(1型,2型)),在具有抗病毒和免疫调节作用的药物治疗前后,即合成化合物(肌苷pranobex)和植物物质(龙骨)。我们对141例乳头瘤病毒和疱疹病毒感染患者进行了肌苷pranobex和龙葵治疗。血清中MMP-2、MMP-9和TIMP-1、TIMP-2的测定采用美国RD诊断公司的特异性试剂。肌苷pranobex和龙葵活性物质的药物治疗与研究中所有组MMP-2, MMP-9和1型和2型组织抑制剂水平的正动态相关。然而,肌苷Pranobex产生更明显的变化,特别是在病毒共感染的亚群中。
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