LL37 inhibits the inflammatory endothelial response induced by viral or endogenous DNA |
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| Affiliation: | 1. Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany;2. Walter Brendel Centre of Experimental Medicine and Munich Heart Alliance, Ludwig Maximilians University München, Germany;3. Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Germany;2. Department of Pediatrics, University of Nevada School of Medicine, Las Vegas, Nevada;3. School of Community Health Sciences, University of Nevada, Las Vegas, Nevada;4. School of Dental Medicine, University of Nevada, Las Vegas, Nevada;5. Department of Endocrinology, Emory University School of Medicine, Atlanta, Georgia;1. Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA;2. Department of Pathology, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA;1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China;2. Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China;3. College of Hydraulic and Hydroelectric Engineering, Sichuan University, Chengdu 610041, China;4. Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing 100000, China;1. Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan;2. Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan;1. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, United States;2. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, United States |
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| Abstract: | In viral infection, morbidity and mortality often result from extrahepatic disease manifestations such as vasculitis. We hereby show that human microvascular endothelial cells express viral receptors of the innate immune system which are induced upon ligand engagement. Furthermore, stimulation of endothelial cells with the synthetic analog of viral DNA, poly (dA:dT), human DNA and hepatitis B virus-containing immunoprecipitates from a patient with polyarteritis nodosa induces an inflammatory response including the upregulation of adhesion molecules, which is mediated exclusively by TLR9 and involves an IRF3-dependent pathway. Thus, endothelial cells are able to actively participate in immune mediated vascular inflammation caused by viral infections. Furthermore, we provide evidence for the ability of LL37 to bind and internalize viral or endogenous DNA into non-immune cells. DNA nucleotides internalized by LL37 suppress the production of proinflammatory mediators suggesting a protective effect against direct responses to viral infection or circulating DNA-fragments of endogenous origin. |
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| Keywords: | DNA LL37 TLR9 Viral |
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