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MiR-155 regulates n...
MiR-155 regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis
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- Hawez, Avin (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital
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- Taha, Dler (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital
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- Algaber, Anwar (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital
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- Madhi, Raed (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital
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- Rahman, Milladur (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital
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- Thorlacius, Henrik (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2022
- 2022
- Engelska.
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Ingår i: Journal of Leukocyte Biology. - 1938-3673. ; 111:2, s. 391-400
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Neutrophil extracellular traps (NETs)-mediated tissue damage is a hallmark in abdominal sepsis. Under certain conditions, microRNAs (miRs) can regulate protein expression and cellular functions. The aim of this study was to investigate the role of miR-155 in sepsis-induced NET formation, lung inflammation, and tissue damage. Abdominal sepsis was induced in wild-type (WT) C57BL/6 and miR-155 gene-deficient mice by cecal ligation and puncture (CLP). The amount of DNA-histone complex formation as well as myeloperoxidase (MPO) and citrullinated histone 3 in neutrophils isolated from bone marrow were examined by ELISA and flow cytometry. NETs were detected by electron microscopy in the septic lung. Levels of PAD4 and citrullinated histone 3 were determined by Western blot in the blood neutrophils. Lung levels of MPO, CXC chemokines, and plasma levels of DNA-histone complexes and CXC chemokines were quantified. In vitro studies revealed that neutrophils from miR-155 gene-deficient mice had less NETs forming ability than WT neutrophils. In the miR-155 gene-deficient mice, CLP yielded much less NETs in the lung tissue compared with WT control. CLP-induced PAD4 levels, histone 3 citrullination, edema, MPO activity, and neutrophil recruitment in the lung were markedly reduced in the mice lacking miR-155. Furthermore, tissue and plasma levels of CXCL1 and CXCL2 were significantly lower in the miR-155 gene-deficient mice compared with WT after induction of abdominal sepsis. Taken together, our findings suggest that miR-155 regulates pulmonary formation of NETs in abdominal sepsis via PAD4 up-regulation and histone 3 citrullination. Thus, targeting miR-155 could be a useful target to reduce pulmonary damage in abdominal sepsis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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