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C5a

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https://www.readbyqxmd.com/read/29773900/c5a-induces-a549-cell-proliferation-of-non-small-cell-lung-cancer-via-gdf15-gene-activation-mediated-by-gcn5-dependent-klf5-acetylation
#1
Chenhui Zhao, Yongting Li, Wen Qiu, Fengxia He, Weiming Zhang, Dan Zhao, Zhiwei Zhang, Erbao Zhang, Pei Ma, Yiqian Liu, Ling Ma, Fengming Yang, Yingwei Wang, Yongqian Shu
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29765378/epithelial-c5ar1-signaling-enhances-uropathogenic-escherichia-coli-adhesion-to-human-renal-tubular-epithelial-cells
#2
Yun Song, Kun-Yi Wu, Weiju Wu, Zhao-Yang Duan, Ya-Feng Gao, Liang-Dong Zhang, Tie Chong, Malgorzata A Garstka, Wuding Zhou, Ke Li
Recent work in a murine model of ascending urinary tract infection has suggested that C5a/C5aR1 interactions play a pathogenic role in the development of renal infection through enhancement of bacterial adhesion/colonization to renal tubular epithelial cells (RTECs). In the present study, we extended these observations to human. We show that renal tubular epithelial C5aR1 signaling is involved in promoting uropathogenic Escherichia coli (UPEC) adhesion/invasion of host cells. Stimulation of primary cultures of RTEC with C5a resulted in significant increases in UPEC adhesion/invasion of the RTEC...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29757426/releasing-the-complement-brakes-is-myeloperoxidase-the-missing-link-between-factor-h-and-c5a-in-anti-neutrophil-cytoplasmic-antibody-vasculitis
#3
Peter Heeringa, Mark Alan Little
No abstract text is available yet for this article.
May 10, 2018: Rheumatology
https://www.readbyqxmd.com/read/29743491/classical-and-alternative-complement-activation-on-photoreceptor-outer-segments-drives-monocyte-dependent-retinal-atrophy
#4
Kenneth J Katschke, Hongkang Xi, Christian Cox, Tom Truong, Yann Malato, Wyne P Lee, Brent McKenzie, Rommel Arceo, Jianhua Tao, Linda Rangell, Mike Reichelt, Lauri Diehl, Justin Elstrott, Robby M Weimer, Menno van Lookeren Campagne
Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29743041/plasma-inflammatory-and-immune-proteins-as-predictors-of-intra-amniotic-infection-and-spontaneous-preterm-delivery-in-women-with-preterm-labor-a-retrospective-study
#5
Hyunsoo Park, Kyo Hoon Park, Yu Mi Kim, Song Yi Kook, Se Jeong Jeon, Ha-Na Yoo
BACKGROUND: We investigated whether various inflammatory and immune proteins in plasma predict intra-amniotic infection and imminent preterm delivery in women with preterm labor and compared their predictive ability with that of amniotic fluid (AF) interleukin (IL)-6 and serum C-reactive protein (CRP). METHODS: This retrospective cohort study included 173 consecutive women with preterm labor who underwent amniocentesis for diagnosis of infection and/or inflammation in the AF...
May 9, 2018: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/29736379/antineutrophil-cytoplasmic-antibody-associated-vasculitides-with-renal-involvement-open-challenges-in-the-remission-induction-therapy
#6
REVIEW
Maurizio Salvadori, Aris Tsalouchos
Renal involvement with rapidly progressive glomerulonephritis is a common manifestation of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides, which is characterized by end-stage renal disease and high mortality rates in untreated and/or late referral patients. The long-term renal survival has improved dramatically since the addition of cyclophosphamide (CYC) and recently of rituximab (RTX) in association with corticosteroids in the remission induction therapeutic regimens. However, renal prognosis remains unfavorable for many patients and the mortality rate is still significantly high...
May 6, 2018: World Journal of Nephrology
https://www.readbyqxmd.com/read/29736038/human-cd45-is-an-f-component-specific-receptor-for-the-staphylococcal-toxin-panton-valentine-leukocidin
#7
Angelino T Tromp, Michiel Van Gent, Pauline Abrial, Amandine Martin, Joris P Jansen, Carla J C De Haas, Kok P M Van Kessel, Bart W Bardoel, Elisabeth Kruse, Emilie Bourdonnay, Michael Boettcher, Michael T McManus, Christopher J Day, Michael P Jennings, Gérard Lina, François Vandenesch, Jos A G Van Strijp, Robert Jan Lebbink, Pieter-Jan A Haas, Thomas Henry, András N Spaan
The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI ) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV...
May 7, 2018: Nature Microbiology
https://www.readbyqxmd.com/read/29734524/complement-system-s-role-in-cancer-and-its-therapeutic-potential-in-ovarian-cancer
#8
REVIEW
Halin Bareke, Julide Akbuga
Cancer immunotherapy is a strong candidate for the long awaited new edition to standard cancer therapies. For an effective immunotherapy, it is imperative to delineate the players of anti-tumor immune response. As an important innate immune system effector mechanism, complement is highly likely to play a substantial role in cancer immunity. Studies suggest that there may be two different 'states of complement' that show opposing effects on cancer cells; a complement profile that has anti-tumor effects with low expression of mCRPs, lytic MAC concentration and moderate C5a concentration, and a complement profile that has protumor effects with high expression of mCRPs, sublytic MAC, and high concentrations of C5a...
May 7, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29729954/complement-activation-in-patients-with-diabetic-nephropathy
#9
X-Q Li, D-Y Chang, M Chen, M-H Zhao
AIM: Emerging evidence has indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN), although the pathways of complement activation and their clinicopathological relevance in DN are as yet unclear. The present study aimed to investigate levels of various complement components in plasma and urine of DN patients, and their correlation with clinicopathological parameters. METHODS: A total of 68 biopsy-proven DN patients with plasma samples were recruited, including 50 patients who also had urine samples available...
April 16, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29724241/systemic-inhibition-of-the-membrane-attack-complex-impedes-neuroinflammation-in-chronic-relapsing-experimental-autoimmune-encephalomyelitis
#10
Iliana Michailidou, Aldo Jongejan, Jeroen P Vreijling, Theodosia Georgakopoulou, Marit B de Wissel, Ruud A Wolterman, Patrick Ruizendaal, Ngaisah Klar-Mohamad, Anita E Grootemaat, Daisy I Picavet, Vinod Kumar, Cees van Kooten, Trent M Woodruff, B Paul Morgan, Nicole N van der Wel, Valeria Ramaglia, Kees Fluiter, Frank Baas
The complement system is a key driver of neuroinflammation. Activation of complement by all pathways, results in the formation of the anaphylatoxin C5a and the membrane attack complex (MAC). Both initiate pro-inflammatory responses which can contribute to neurological disease. In this study, we delineate the specific roles of C5a receptor signaling and MAC formation during the progression of experimental autoimmune encephalomyelitis (EAE)-mediated neuroinflammation. MAC inhibition was achieved by subcutaneous administration of an antisense oligonucleotide specifically targeting murine C6 mRNA (5 mg/kg)...
May 3, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29721926/anaphylatoxin-signaling-in-retinal-pigment-and-choroidal-endothelial-cells-characteristics-and-relevance-to-age-related-macular-degeneration
#11
Bärbel Rohrer
Age-related macular degeneration (AMD) is the leading cause of blindness in the USA. Polymorphisms in various complement components are associated with an increased risk for AMD, and it has been hypothesized that an overactive complement system is partially responsible for the pathology of AMD. AMD is classified as early, intermediate, or late AMD, depending on the degree of the associated pathologies. Late AMD can be characterized as either lesions associated with neovascular AMD or geographic atrophy. Both sets of lesions are associated with pathology at the RPE/choroid interface, which include a thickening of Bruch's membrane, presence of drusen, and pigmentary alterations, and deterioration of the blood-retina barrier has been reported...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29718732/avacopan-in-the-treatment-of-anca-associated-vasculitis
#12
Vladimir Tesar, Zdenka Hruskova
ANCA-associated vasculitis (AAV) is a rare but potentially life-threatening disease. Currently used induction treatment (cyclophosphamide or rituximab with high-dose corticosteroids) has significantly improved outcome of AAV, but is associated with high toxicity. Alternative complement pathway activation was shown to play a role in the pathogenesis of AAV, thus providing rationale for the use of avacopan, a selective inhibitor of C5a receptor, in the treatment of AAV. Areas Covered: Pharmacokinetic and pharmocodynamic properties of avacopan, clinical efficacy and safety and tolerability of avacopan in so far performed clinical trials in patients with AAV are reviewed and discussed...
May 2, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29710512/anaphylatoxin-c5a-induces-inflammation-and-reduces-insulin-sensitivity-by-activating-tlr4-nf-kb-pi3k-signaling-pathway-in-3t3-l1-adipocytes
#13
Xin-Yan Zhang, Yan Liu, Ting He, Ting-Ting Yang, Jing Wu, Katherine Cianflone, Hui-Ling Lu
Obesity closely correlates with metaflammation and characterizes with systemic-chronic-low inflammation. This study aims to evaluate effects of C5a on the inflammatory response and insulin resistance in 3T3-L1 adipocytes. 3T3-L1 pre-adipocytes were induced to the mature 3T3-L1 adipocytes. Then, 3T3-L1 were intervened with anaphylatoxin C5a, lipopolysaccharide (LPS) and C5a + LPS, respectively. Levels of Omentin, Chemerin, Vaspin and Apelin 12 in supernatants of medium were examined using ELISA. C5L2, C5a receptor (C5aR), I kappa B (IkB), IkB kinase (IKK), insulin receptor substrate 1 (IRS-1), IRS-2, PI3 K, p-PI3 K and β-actin were examined using RT-PCR and western blot assay, respectively...
April 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29691378/blockade-of-the-c5a-c5ar-axis-alleviates-lung-damage-in-hdpp4-transgenic-mice-infected-with-mers-cov
#14
Yuting Jiang, Guangyu Zhao, Nianping Song, Pei Li, Yuehong Chen, Yan Guo, Junfeng Li, Lanying Du, Shibo Jiang, Renfeng Guo, Shihui Sun, Yusen Zhou
The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage...
April 24, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29686667/-streptococcus-agalactiae-non-pilus-cell-wall-anchored-proteins-involvement-in-colonization-and-pathogenesis-and-potential-as-vaccine-candidates
#15
REVIEW
Giampiero Pietrocola, Carla Renata Arciola, Simonetta Rindi, Lucio Montanaro, Pietro Speziale
Group B Streptococcus (GBS) remains an important etiological agent of several infectious diseases including neonatal septicemia, pneumonia, meningitis, and orthopedic device infections. This pathogenicity is due to a variety of virulence factors expressed by Streptococcus agalactiae . Single virulence factors are not sufficient to provoke a streptococcal infection, which is instead promoted by the coordinated activity of several pathogenicity factors. Such determinants, mostly cell wall-associated and secreted proteins, include adhesins that mediate binding of the pathogen to host extracellular matrix/plasma ligands and cell surfaces, proteins that cooperate in the invasion of and survival within host cells and factors that neutralize phagocytosis and/or modulate the immune response...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29685955/apigenin-inhibits-c5a-induced-proliferation-of-human-nasopharyngeal-carcinoma-cells-through-down-regulation-of-c5ar
#16
Yanshu Zhang, Ying Cao, Linlin Zhang, Chunyan Feng, Guangquan Zhou, Guohua Wen
C5a is able to induce the proliferation of human nasopharyngeal carcinoma (NPC) cells. Therefore, an effective method or drug that can specifically inhibit C5a-induced proliferation of human NPC cells needs to developed. Reportedly, Apigenin has anti-proliferative effects on a variety of cancer cells. However, the effect of Apigenin on NPC cell proliferation and its underlying mechanism are still unclear. Herein, this study aimed to evaluate the effect of Apigenin on C5a-induced proliferation of human NPC cells and its possible mechanism through down-regulation of C5aR...
April 23, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29683202/placental-inflammation-in-pre-eclampsia-by-nod-like-receptor-protein-nlrp-3-inflammasome-activation-in-trophoblasts
#17
G S Stødle, G B Silva, L H Tangerås, L M Gierman, I Nervik, U E Dahlberg, C Sun, M H Aune, L C V Thomsen, L Bjørge, A-C Iversen
Pre-eclampsia is associated with increased levels of cholesterol and uric acid and an inflamed placenta expressing danger-sensing pattern recognition receptors (PRRs). Crystalline cholesterol and uric acid activate the PRR Nod-like receptor protein (NLRP)3 inflammasome to release interleukin (IL)-1β and result in vigorous inflammation. We aimed to characterize crystal-induced NLRP3 activation in placental inflammation and examine its role in pre-eclampsia. We confirmed that serum total cholesterol and uric acid were elevated in pre-eclamptic compared to healthy pregnancies and correlated positively to high sensitivity C-reactive protein (hsCRP) and the pre-eclampsia marker soluble fms-like tyrosine kinase-1 (sFlt-1)...
April 23, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29677088/corrigendum-the-priming-effect-of-c5a-on-monocytes-is-predominantly-mediated-by-the-p38-mapk-pathway
#18
(no author information available yet)
No abstract text is available yet for this article.
April 19, 2018: Shock
https://www.readbyqxmd.com/read/29621732/c5a-receptor1-inhibition-alleviates-influenza-virus-induced-acute-lung-injury
#19
Nianping Song, Pei Li, Yuting Jiang, Hong Sun, Jing Cui, Guangyu Zhao, Dan Li, Yan Guo, Yuehong Chen, Jimin Gao, Shihui Sun, Yusen Zhou
Influenza A virus is an important human pathogen that causes 3 to 5 million severe cases of influenza worldwide each year. An aberrant innate immune response, particularly hypercytokinemia, is thought to play an important role in the disease, although the pathogenesis of severe influenza virus infection remains unclear and no specific and efficacious immunotherapy is available. This study reports dysregulated complement activation in mice after infection with A/Puerto Rico/8/34 (PR8). C5aR1-deficient mice and mice treated with an anti-C5aR1 antibody were used as models to study the C5a-C5aR1 axis during acute lung injury (ALI) induced by influenza virus infection...
April 2, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29616034/specific-inhibition-of-complement-activation-significantly-ameliorates-autoimmune-blistering-disease-in-mice
#20
Sidonia Mihai, Misa Hirose, Yi Wang, Joshua M Thurman, V Michael Holers, B Paul Morgan, Jörg Köhl, Detlef Zillikens, Ralf J Ludwig, Falk Nimmerjahn
Epidermolysis bullosa acquisita (EBA) is an antibody-mediated blistering skin disease associated with tissue-bound and circulating autoantibodies to type VII collagen (COL7). Transfer of antibodies against COL7 into mice results in a subepidermal blistering phenotype, strictly depending on the complement component C5. Further, activation predominantly by the alternative pathway is required to induce experimental EBA, as blistering was delayed and significantly ameliorated only in factor B-/- mice. However, C5 deficiency not only blocked the activation of terminal complement components and assembly of the membrane attack complex (MAC) but also eliminated the formation of C5a...
2018: Frontiers in Immunology
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