Sultana Sahin, Adhikary Rana, Nandi Ajeya, Bishayi Biswadev
Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, India.
Microb Pathog. 2016 Oct;99:148-161. doi: 10.1016/j.micpath.2016.08.021. Epub 2016 Aug 21.
Matrix metalloproteinases (MMPs) are crucial players in Staphylococcus aureus mediated synovial tissue destruction in the pathogenesis of septic arthritis. Bacterial insult increases proteolytic matrix fragments by activated chondrocytes and synovial fibroblasts leading to induction of matrix metalloproteinases. Tissue destruction via MMPs induced by bacterial products, necrotic tissues and proinflammatory cytokines have been reported. Cytokines like TNF-α, IL-1β released from host cells in response to S. aureus infection promote cartilage degradation by stimulating the production of MMPs. Antibiotic treatment can eradicate invading bacteria but elevated levels of cytokines and cytokines induced MMPs activation lead to progressive and devastating bone and cartilage destruction even after bacterial clearance. Like other MMPs, MMP-2 also contributes to extracellular matrix degradation in different types of arthritis. Release of certain pro inflammatory cytokines can also be regulated by MMP-2 activation leading to further tissue destruction. The role of MMP-2 in the pathogenesis of S. aureus infection induced septic arthritis and its influence on cytokines regulation needs further investigation. Whether neutralization of MMP-2 provides protection against Staphylococcus aureus infection induced septic arthritis in mice is an obvious question. Here we reported that neutralization of MMP-2 during S. aureus infection induced septic arthritis might be beneficial for preventing infection induced extracellular matrix destruction thereby decreasing bacterial burden in synovial tissues and regulating inflammatory cytokines in arthritic mice.
基质金属蛋白酶(MMPs)在金黄色葡萄球菌介导的化脓性关节炎发病机制中滑膜组织破坏过程中起着关键作用。细菌侵袭会增加活化软骨细胞和滑膜成纤维细胞产生的蛋白水解性基质片段,从而导致基质金属蛋白酶的诱导。已有报道称,细菌产物、坏死组织和促炎细胞因子诱导的基质金属蛋白酶会导致组织破坏。宿主细胞因金黄色葡萄球菌感染而释放的细胞因子,如肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β),通过刺激基质金属蛋白酶的产生促进软骨降解。抗生素治疗可以根除入侵细菌,但即使在细菌清除后,细胞因子水平升高以及细胞因子诱导的基质金属蛋白酶激活仍会导致进行性且具有破坏性的骨和软骨破坏。与其他基质金属蛋白酶一样,MMP-2也在不同类型的关节炎中导致细胞外基质降解。MMP-2的激活还可调节某些促炎细胞因子的释放,从而导致进一步的组织破坏。MMP-2在金黄色葡萄球菌感染诱导的化脓性关节炎发病机制中的作用及其对细胞因子调节的影响需要进一步研究。MMP-2的中和是否能为小鼠提供针对金黄色葡萄球菌感染诱导的化脓性关节炎的保护是一个显而易见的问题。在此我们报道,在金黄色葡萄球菌感染诱导的化脓性关节炎期间中和MMP-2可能有助于预防感染诱导的细胞外基质破坏,从而降低滑膜组织中的细菌负荷并调节关节炎小鼠中的炎性细胞因子。