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Protease and inflammation

Jingjing Cai, Hong Yuan, Huan Yang, Timothy R Billiar, Alex F Chen
OBJECTIVE: The mechanism of sterile inflammatory response drive the development of vessle remodeling and intimal hyperplasia (IH) was not fully understood. We hypothesis that myeloid differentiation protein-88 (MyD88) in macrophages, the major endocellular adaptor molecule that mediate most toll like receptors (TLRs) induced inflammation, activates processes leading to vessle remodeling via upregulation of cathepsin L activity. DESIGN AND METHOD: Carotid artery wire injury was applied in C57BL/6 wild type (WT) mice, MyD88 mice, Lyz-MyD88 mice and cathepsin L mice to investigate vessel remodeling and intimal formation...
September 2016: Journal of Hypertension
Ye Cao, Kai Guan, Xiang He, Congwen Wei, Zirui Zheng, Yanhong Zhang, Shengli Ma, Hui Zhong, Wei Shi
The Yersinia outer protein J (YopJ) plays a pivotal role in evading the host immune response and establishes a persistent infection in host cells after bacterial infection. YopJ is a cysteine protease and can act as a deubiquitinating enzyme that deubiquitinates several targets in multiple signaling pathways. Stimulator of interferon genes (STING) is a critical adapter for the induction of interferon regulatory factor 3 (IRF3) phosphorylation and subsequent production of the cytokines in response to nucleic acids in the cytoplasm...
October 11, 2016: Biochimica et Biophysica Acta
I Tuleta, F Stöckigt, U R Juergens, C Pizarro, J W Schrickel, G Kristiansen, G Nickenig, D Skowasch
INTRODUCTION: Intermittent hypoxia as a surrogate of obstructive sleep apnea is associated with different cardiovascular complications. However, the effects of intermittent hypoxia on the lung tissue are less known. Therefore, the aim of our present study was to investigate if intermittent hypoxia may influence oxidative stress, inflammation, and protease/antiprotease system in the lung. Additionally, potential protective properties of anti-inflammatory and anti-oxidative drugs have been evaluated...
October 13, 2016: Lung
Tong-Cui Ma, Run-Hong Zhou, Xu Wang, Jie-Liang Li, Ming Sang, Li Zhou, Ke Zhuang, Wei Hou, De-Yin Guo, Wen-Zhe Ho
The Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, is known to have anti-inflammatory effect in both in vitro and in vivo systems. Macrophages play a key role in inflammation and immune activation, which is implicated in HIV disease progression. Here, we investigated the effect of BBI on HIV infection of peripheral blood monocyte-derived macrophages. We demonstrated that BBI could potently inhibit HIV replication in macrophages without cytotoxicity. Investigation of the mechanism(s) of BBI action on HIV showed that BBI induced the expression of IFN-β and multiple IFN stimulated genes (ISGs), including Myxovirus resistance protein 2 (Mx2), 2',5'-oligoadenylate synthetase (OAS-1), Virus inhibitory protein (viperin), ISG15 and ISG56...
October 13, 2016: Scientific Reports
Arthitaya Meeprasert, Supot Hannongbua, Nawee Kungwan, Thanyada Rungrotmongkol
Hepatitis C virus (HCV) is a serious cause of liver inflammation, cirrhosis and the development of hepatocellular carcinoma. Its NS3/4A serine protease functions to cleave a specific peptide bond, which is an important step in HCV replication. Thus the NS3/4A protease has become one of the main drug-targets in the design and development of anti-HCV agents. Unfortunately, high mutation rates in HCV have been reported due to the lack of RNA proofreading activity resulting in drug resistance. Herein, all-atom molecular dynamics simulations were employed to understand and illustrate the effects of the NS3/4A D168V mutation on faldaprevir (FDV) and danoprevir (DNV) binding efficiency...
October 12, 2016: Molecular BioSystems
Tobias Feldreich, Axel C Carlsson, Ulf Risérus, Anders Larsson, Lars Lind, Johan Ärnlöv
BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality. METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10...
September 17, 2016: Atherosclerosis
Xiang Xu, John R Greenland, Jeffrey E Gotts, Michael A Matthay, George H Caughey
Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl-/- mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl+/+ mice...
2016: PloS One
André Struglics, Marcin Okroj, Per Swärd, Richard Frobell, Tore Saxne, L Stefan Lohmander, Anna M Blom
BACKGROUND: The complement system is suggested to be involved in the pathogenesis of osteoarthritis (OA), and proinflammatory cytokines may play a role in OA development by inducing proteases. The association between complement factors, cytokines and OA has not been investigated. The aim of the present study was to explore the involvement of the complement system after knee trauma and in OA. METHODS: C4d, C3bBbP and soluble terminal complement complex (sTCC) resulting from complement activation were immunoassayed in synovial fluid from subjects with healthy knees (reference), OA, rheumatoid arthritis (RA; positive control), pyrophosphate arthritis (PPA; positive control) and knee injury; other biomarkers were previously assessed...
October 6, 2016: Arthritis Research & Therapy
Zela Keuylian, Alain Hovnanian
Protease regulation plays a crucial role in skin homeostasis and inflammation as revealed by the identification of loss-of-function mutations in SPINK5 (serine protease inhibitor of Kazal type 5) in Netherton sydrome (NS). SPINK5 encodes LEKTI (lympho-epithelial Kazal type related inhibitor), a multi-domain serine protease inhibitor expressed in all stratified epithelia. Our laboratory has developed a number of murine models which have been instrumental to dissecting the pathogenesis of NS. This mini-review discusses the major findings of these models and emphasizes the role of protease regulation, especially Kallikrein related peptidases in NS...
October 6, 2016: Biological Chemistry
Anna-Karin Olsson, Jessica Cedervall
It has become increasingly clear that circulating immune cells in the body have a major impact on cancer development, progression, and outcome. The role of both platelets and neutrophils as independent regulators of various processes in cancer has been known for long, but it has quite recently emerged that the platelet-neutrophil interplay is yet a critical component to take into account during malignant disease. It was reported a few years ago that neutrophils in mice with cancer have increased propensity to form neutrophil extracellular traps (NETs) - web-like structures formed by externalized chromatin and secreted proteases...
2016: Frontiers in Immunology
Y X Wang, M L Ji, C Y Jiang, Z B Qian
Chronic obstructive pulmonary disease (COPD) is a devastating lung disorder characterized by sustained airway flow restriction that is not fully reversible. The precise pathogenic mechanisms are unknown, but it is clear that cigarette smoking and chronic inflammatory stimulation are the major causes of COPD. Lung inflammation associated with COPD involves multiple cytokines, aggregation, and activation of neutrophils in the airway and lung tissue, and release of proteases and oxygen free radicals. In this study, a rat model of COPD was established by daily cigarette smoke exposure plus endotoxin treatment (the experimental group)...
August 19, 2016: Genetics and Molecular Research: GMR
Sahera Dirajlal-Fargo, Carlee Moser, Todd T Brown, Theodoros Kelesidis, Michael P Dube, James H Stein, Judith Currier, Grace A McComsey
Background.  Antiretroviral therapy (ART) can alter glucose metabolism, but little data exist on the association of raltegravir (RAL) with insulin resistance. Methods.  A5260s was a substudy of A5257, a prospective open-label randomized trial in which human immunodeficiency virus (HIV)-infected treatment-naive participants were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or RAL over 96 weeks. Baseline and changes in insulin resistance as estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) were assessed...
September 2016: Open Forum Infectious Diseases
Tolunay Beker Aydemir, Catalina Troche, Min-Hyun Kim, Robert J Cousins
Zinc influences signaling pathways through controlled targeted zinc transport. Zinc transporter Zip14 KO mice display a phenotype which includes impaired intestinal barrier function with low-grade chronic inflammation, hyperinsulinemia and increased body fat which are signatures of diet-induced diabetes (type 2 diabetes) and obesity in humans. Hyperglycemia in type 2 diabetes and obesity is caused by insulin resistance. Insulin resistance results in inhibition of glucose uptake by liver and other peripheral tissues, principally adipose and muscle and with concurrently higher hepatic glucose production...
October 4, 2016: Journal of Biological Chemistry
Hiroaki Kimura, Tadayoshi Karasawa, Fumitake Usui, Akira Kawashima, Yuka Endo, Motoi Kobayashi, Ai Sadatomo, Jun Nakamura, Yusaku Iwasaki, Toshihiko Yada, Hiroko Tsutsui, Tadashi Kasahara, Masafumi Takahashi
Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1β and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship of remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat diet-induced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue...
October 4, 2016: American Journal of Physiology. Endocrinology and Metabolism
Qiao-Qing Zhong, Xiang Wang, Yun-Feng Li, Li-Jun Peng, Zhi-Sheng Jiang
Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, which was most commonly examined in mucosal fluids such as saliva, is a versatile molecule and plays non-redundant roles. In addition to its anti-protease activity, SLPI has been shown to express anti-bacterial, anti-viral, anti-fungal, and anti-inflammatory properties as well as participating in innate and adaptive immune responses, most of which has been well documented. Recently, it is reported that SLPI is expressed in adipocytes and adipose tissue where it could play an important feedback role in the resolution of inflammation...
October 3, 2016: Experimental Biology and Medicine
Marcin Surmiak, Marek Sanak
BACKGROUND: One of characteristic findings in granulomatosis with polyangiitis (GPA) is the presence of proteinase-3 (anti-PR3) specific antibodies. These antibodies can cause neutrophil activation, degranulation and generation of reactive oxygen species (ROS). Each of these inflammatory events can be suppressed by circulating alpha-1 antitrypsin (A1AT). A1AT is an acute phase protein increasing during inflammation, however, it may circulate as an inactive polymeric protein. AIM OF THE STUDY: The aim was to analyze how different types of A1AT can affect anti-PR3 mediated neutrophil activation...
August 5, 2016: Pharmacological Reports: PR
Yayoi Kamata, Utako Kimura, Hironori Matsuda, Suhandy Tengara, Atsuko Kamo, Yoshie Umehara, Kyoichi Iizumi, Hiroaki Kawasaki, Yasushi Suga, Hideoki Ogawa, Mitsutoshi Tominaga, Kenji Takamori
BACKGROUND: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H1-antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. OBJECTIVE: This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients...
September 15, 2016: Journal of Dermatological Science
Raffaele Simeoli, Giuseppina Mattace Raso, Claudio Pirozzi, Adriano Lama, Anna Santoro, Roberto Russo, Trinidad Montero-Melendez, Roberto Berni Canani, Antonio Calignano, Mauro Perretti, Rosaria Meli
BACKGROUND AND PURPOSE: Butyrate has shown benefits in inflammatory bowel diseases (IBD). However, its oral administration is infrequent due to rancid smell and unpleasant taste. The efficacy of a more palatable butyrate-releasing derivative, N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), was evaluated in a mouse model of colitis induced by dextran sodium sulphate (DSS). EXPERIMENTAL APPROACH: Male 10-week-old BALB/c mice received DSS (2.5%) in drinking water (for 5d) followed by DSS-free water for 7d (DSS group)...
September 29, 2016: British Journal of Pharmacology
Linda R Klei, Dong Hu, Robert Panek, Danielle N Alfano, Rachel E Bridwell, Kelly M Bailey, Katherine I Oravecz-Wilson, Vincent J Concel, Emily M Hess, Matthew Van Beek, Phillip C Delekta, Shufang Gu, Simon C Watkins, Adrian T Ting, Peter J Gough, Kevin P Foley, John Bertin, Linda M McAllister-Lucas, Peter C Lucas
Microvascular endothelial cells maintain a tight barrier to prevent passage of plasma and circulating immune cells into the extravascular tissue compartment, yet endothelial cells respond rapidly to vasoactive substances, including thrombin, allowing transient paracellular permeability. This response is a cornerstone of acute inflammation, but the mechanisms responsible are still incompletely understood. Here, we demonstrate that thrombin triggers MALT1 to proteolytically cleave cylindromatosis (CYLD). Fragmentation of CYLD results in microtubule disruption and a cascade of events leading to endothelial cell retraction and an acute permeability response...
September 27, 2016: Cell Reports
Lingling Xuan, Rentao Jiang, Zhiyuan Wu, Honggan Yi, Chunsuo Yao, Qi Hou, Chunfeng Qu
BACKGROUND: Chronic inflammation is one of the important mediators of colitis-related colon cancer (CRC). Abundant mast cells (MCs) were observed in the tumor microenvironment and mediators released upon MC activation play an important role in the process of chronic inflammation. Previously, we found that activation of intestine mucosal MCs recruited and modulated the inflammatory CD11b(+)Gr1(+) cells to promote the CRC development. In the current study we investigated the effects of Vam3, a resveratrol dimer with potent anti-inflammatory effects, on CRC development...
2016: Frontiers in Pharmacology
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