Cyclic Compression of Chondrocytes Counteracts Pro-Inflammatory Tissue Remodeling Induced by Interleukin-1

Author(s):  
A. E. DiTullio ◽  
S. Park ◽  
P. A. Torzilli ◽  
C. T. Chen

Chondrocytes in tissue engineered constructs face challenging environments when first transplanted into a synovial joint, including high levels of compression/shear and pro-inflammatory cytokines. The joint level of interleukin 1 (IL-1) after trauma injury and in a repaired joint is acutely elevated. Matrix remodeling in tissue engineered constructs can be easily affected by the elevation and activation of aggrecanases (ADAMTS-4 and ADAMTS-5) and matrix metalloproteinases (MMPs) [2–4, 7–9, 11]. Several recent studies suggest that tensile loading and unconfined compression of chondrocytes has some anti-inflammatory effects against interleukin 1 (IL-1) by the downregulation of COX-2 and iNOS genes [1, 5, 6]. However, the role of loading in tissue repair at physiological levels is not clear. The objective of this study was to determine the effect of cyclic confined compression on the gene expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in agarose-embedded chondrocytes in the presence of interleukin 1 (IL-1).

Author(s):  
Carrie H. Ling ◽  
Janice H. Lai ◽  
James F. Nishimuta ◽  
Marc E. Levenston

Despite a growing recognition that meniscal degeneration often precedes cartilage degeneration in the development of knee osteoarthritis (OA), little is known about the role of meniscal degeneration in the onset and progression of knee OA. Even a mild degenerative lesion increases meniscal extrusion, implying changes in biomechanical function. Understanding the mechanisms of meniscal degeneration may enable the diagnosis and disease-modifying treatment of early knee OA, potentially preventing or slowing the progression of the disease. The roles of pro-inflammatory cytokines such as interleukin-1 (IL-1) in promoting cartilage matrix degradation and mediating inflammation in the progression of OA have been widely demonstrated [1,2]. Recent results from our group indicated that 20ng/ml hrIL-1α produced similar cell-mediated degradation and loss of mechanical properties in immature cartilage and meniscus, but progresses more rapidly in meniscus explants [3]. This study further explored the effects of IL-1α dosage and medial-lateral differences on the functional degradation of meniscal explants.


Author(s):  
Valerie M. Wolfe ◽  
Seonghun Park ◽  
Marjana Tomic ◽  
Peter A. Torzilli ◽  
C. T. Christopher Chen

Pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), can induce cartilage degradation after acute injury or in inflammatory diseases [1,2,3,7]. The degradative events are coordinated through the elevation and activation of two classes of enzymes, namely matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS-4 and −5) [1,6]. Prior studies suggested that pro-inflammatory responses induced by IL-1β can be inhibited by tensile load [2] and more recently by cyclic compression [8]. It is, however, not clear whether load affects other cytokines, such as TNF-α. TNF-α is known to bind its receptor (TNFR1) to cause a cascade that ends with degradation of an inhibitor, IκBα, and release of the transcription factor NF-κB [3]. The actions of TNF-α are also known to be affected by at least three NF-κB independent pathways including the p38, ERK, and JNK pathways [4]. The objective of this study was to determine whether cyclic compression could affect TNF-α induced cartilage degradation and to determine the roles of p38, ERK, and JNK pathways in TNF-induced cartilage degradation. We hypothesized that cyclic loading would inhibit the degradative effects caused by TNF-α.


Author(s):  
Meghana Kashyap ◽  
Kristen T. Carter ◽  
Brent C. Sauer ◽  
Christopher T. Chen

Chondrocyte death, induced by impact injury (necrosis) and/or apoptotic inducers such as cytokines, and high level of nitric oxide, is important for the development of post-traumatic arthritis (PTA) [1–3]. The upregulation of pro-inflammatory cytokines, such as interleukin −1 (IL-1) and Tumor necrosis factor (TNF) α, is known to mediate cartilage degradation in inflammatory diseases and after trauma injury [1,2, 6–9]. IL-1 induces the degradation of proteoglycan (PG) in cartilage through NF-κB and Mitogen-activated protein kinases (MAPK: p38, ERK and JNK) pathways [1,2,6]. IL-1 is highly upregulated in synovial joint after impact injury, but the role of IL-1 induced chondrocyte death and matrix/PG degradation in injured cartilage is not completely clear.


2021 ◽  
Vol 9 (F) ◽  
pp. 238-245
Author(s):  
Cahyono Hadi ◽  
Jethro Budiman ◽  
Awal Prasetyo ◽  
Cipta Pramana

BACKGROUND: Ectopic pregnancy (EP) is the implantation of an embryo outside the eutopic cavity with the most location of EP is in the fallopian tube (FT), known as tubal EP (TEP). The FT of TEP expresses higher levels of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and IL-8. AIM: The study aimed to look systematically into the current literature and carefully analyze the results to explore the role of IL in EP. METHODS: Three independent reviewers conducted the literature search through some electronic databases searching for articles fulfilling inclusion and exclusion criteria. The lead author independently assessed the risk of bias of each of the 313 articles identified in database searching, 12 articles met the criteria for this review. CONCLUSION: IL-6 and IL-8 have diagnostic significance in predicting EP with the cutoff levels of IL-6 and IL-8 which were 26.48 and 40 pg/mL. Further, research is needed for the role of other interleukins in EP.


2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.


2016 ◽  
pp. 73-76
Author(s):  
B.M. Ventskivskiy ◽  
◽  
I.V. Poladych ◽  
S.O. Avramenko ◽  
◽  
...  

In recent years there has been an increase in the frequency of multiple pregnancies and the associated perinatal losses. It is a result of multiple pregnancy in ART refers to a high-risk gestation, at which premature births occur in 2 times more often than in singleton pregnancies. The objective: to determine the role of pro-inflammatory cytokines in the pathogenesis of premature labor in multiple pregnancy, as a result of assisted reproductive technology. Patients and methods. to determine the pro-inflammatory cytokines that all pregnant with bagtopliddyam held immunosorbent assay, defined concentrations of interleukin (IL) in serum and cervical mucus. Results. The analysis of the levels of pro-inflammatory cytokines (IL-1, IL-8) in the test environment, found high concentrations in the surveyed women with multiple pregnancy, due to the use of ART, compared with spontaneous multiple and singleton pregnancy. Increased concentration of proinflammatory cytokines in patients with multiple pregnancy by ART is associated with their synthesis at the system level, it stimulated foci of inflammation in the female genitals and extragenital localization. This correlates with the clinical data and statistical analysis, patients with multiple pregnancy as a result of ART had weighed infectious-inflammatory history. Conclusion. The study showed that elevated levels of proinflammatory cytokines in the systemic and local level in patients with multiple pregnancy due to ART, typical for women with miscarriage, because of the physiological course of pregnancy characterized by the predominance of anti-inflammatory cytokines that prevent rejection of the fetus as a foreign factor. Based on the data obtained proved the role of systemic inflammatory factors in the genesis of preterm labor in women with a multiple pregnancy, as a result of assisted reproductive technology. Key words: multiple pregnancy, assisted reproductive technology, premature birth, interleukine-1, interleukine-8.


Author(s):  
Е.В. Маркелова ◽  
О.В. Овчинникова ◽  
А.С. Хохлова ◽  
Л.П. Догадова ◽  
А.В. Костюшко ◽  
...  

Оперативное вмешательство - один из основных методов лечения глаукомы. Однако развитие избыточного рубцевания созданных путей оттока определяет результат хирургического лечения в отдаленные сроки. Процессы рубцевания на данный момент недостаточно изучены. Цель исследования - оценка роли матриксной металлопротеиназы-9, ее ингибиторов в процессах рубцевания у больных с первичной открытоугольной глаукомой после оперативного лечения. Методика. Для выявления возможных маркеров избыточного рубцевания методом твердофазного иммуноферментного анализа определяли содержание матриксных металлопротеиназ-9, тканевых ингибиторов металлопротеиназ 2 и -3 в слезной жидкости у 37 пациентов с активной стадией первичной остроугольной глаукомы в динамике послеоперационного периода. Средний возраст пациентов составил 52,8 лет. В зависимости от исхода оперативного вмешательства все пациенты были разделены на 2 группы - с благоприятным исходом (без избыточного рубцевания) и с неблагоприятным исходом (с избыточным рубцеванием) на месте сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Группа контроля включала 20 человек в возрасте от 50 до 66 лет без сопутствующей офтальмологической и соматической патологии в стадии обострения. Результаты. В динамике показано изменение концентрации матриксной металлопротеиназы-9 и ее ингибиторов в послеоперационном периоде. Анализ данных свидетельствует об обратной зависимости уровня матриксной металлопротеиназы-9 и тканевых ингибиторов металлопротеиназы 2 и 3 типов с исходом операции - чем выше концентрация металлопротеиназы-9 и ниже концентрация тканевых ингибиторов металлопротеиназ 2, -3 в слезной жидкости, тем выше вероятность неблагоприятного исхода в виде рубцевания сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Заключение. Мониторинг уровня металлопротеиназ и их тканевых ингибиторов после проведения хирургического лечения пациентов с первичной открытоугольной глаукомой позволяет прогнозировать раннее рубцевание, дает возможность разработки новых методов лечения как в раннем, так и в позднем послеоперационном периоде. Surgery is one of the major treatments for glaucoma; however excessive scarring of created outflow patways affects the long-term outcome. At the present time, scarring processes are not sufficiently studied. Aim. To evaluate the role of matrix metalloproteinase 9 and its inhibitors in scarring after surgical treatment of open-angle glaucoma. Methods. Concentrations of matrix metalloproteinase 9 and tissue inhibitors of metalloproteinases 2 and 3 were measured in tear fluid of 37 patients (mean age, 52.8) with active primary open-angle glaucoma in dynamics during the postoperative period to identify possible markers of excessive scarring. Based on the surgery outcome, all patients were divided into two groups, with a favorable outcome (without excessive scarring) and an unfavorable outcome (with excessive scarring) in the created additional outflow pathways for the intraocular fluid in the postoperative period. The control group included 20 subjects aged 50-66 without eye disease or somatic disease at exacerbation stage. Results. Analysis of changes in concentrations of matrix metalloproteinase 9 and its inhibitors in the postoperative period showed their inverse relationship with the surgery outcome. The higher was the metalloproteinase 9 level and the lower the level of tissue inhibitors of metalloproteinases 2 and 3 the higher was the probability of unfavorable outcome evident as excessive scarring of the formed additional pathways for tear fluid outflow in the postoperative period. Conclusion. Postoperative monitoring of metalloproteinases and their tissue inhibitors allows to predict early scarring and to develop new treatments both in early and late postoperative periods.


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