Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

Giacomo Gravina; Maryam Ardalan; Tetyana Chumak; Anders K. Nilsson; Joakim C. Ek; Hanna Danielsson; Pernilla Svedin; Milos Pekny; Marcela Pekna; Karin Sävman; Ann Hellström; Carina Mallard

doi:10.1016/j.isci.2023.107217

Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

Giacomo Gravina, Maryam Ardalan, Tetyana Chumak, Anders K. Nilsson, Joakim C. Ek, Hanna Danielsson, Pernilla Svedin, Milos Pekny, Marcela Pekna, Karin Sävman, Ann Hellström, Carina Mallard^*

^*Corresponding author for this work

Department of Clinical Medicine - Translational Neuropsychiatry Unit

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

4 Citations (Scopus)

Abstract

Staphylococcus (S.) epidermidis is the most common nosocomial coagulase-negative staphylococci infection in preterm infants. Clinical signs of infection are often unspecific and novel markers to complement diagnosis are needed. We investigated proteomic alterations in mouse brain after S. epidermidis infection and in preterm infant blood. We identified lipocalin-2 (LCN2) as a crucial protein associated with cerebrovascular changes and astrocyte reactivity in mice. We further proved that LCN2 protein expression was associated with endothelial cells but not astrocyte reactivity. By combining network analysis and differential expression approaches, we identified LCN2 linked to blood C-reactive protein levels in preterm infants born <28 weeks of gestation. Blood LCN2 levels were associated with similar alterations of cytokines and chemokines in both infected mice and human preterm infants with increased levels of C-reactive protein. This experimental and clinical study suggests that LCN2 may be a marker of preterm infection/inflammation associated with cerebrovascular changes and neuroinflammation.

Original language	English
Article number	107217
Journal	iScience
Volume	26
Issue	7
Number of pages	24
ISSN	2589-0042
DOIs	https://doi.org/10.1016/j.isci.2023.107217
Publication status	Published - Jul 2023

Keywords

Immunology
Neurology
Proteomics

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Gravina, G., Ardalan, M., Chumak, T., Nilsson, A. K., Ek, J. C., Danielsson, H., Svedin, P., Pekny, M., Pekna, M., Sävman, K., Hellström, A., & Mallard, C. (2023). Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants. iScience, 26(7), Article 107217. https://doi.org/10.1016/j.isci.2023.107217

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title = "Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants",

abstract = "Staphylococcus (S.) epidermidis is the most common nosocomial coagulase-negative staphylococci infection in preterm infants. Clinical signs of infection are often unspecific and novel markers to complement diagnosis are needed. We investigated proteomic alterations in mouse brain after S. epidermidis infection and in preterm infant blood. We identified lipocalin-2 (LCN2) as a crucial protein associated with cerebrovascular changes and astrocyte reactivity in mice. We further proved that LCN2 protein expression was associated with endothelial cells but not astrocyte reactivity. By combining network analysis and differential expression approaches, we identified LCN2 linked to blood C-reactive protein levels in preterm infants born <28 weeks of gestation. Blood LCN2 levels were associated with similar alterations of cytokines and chemokines in both infected mice and human preterm infants with increased levels of C-reactive protein. This experimental and clinical study suggests that LCN2 may be a marker of preterm infection/inflammation associated with cerebrovascular changes and neuroinflammation.",

keywords = "Immunology, Neurology, Proteomics",

author = "Giacomo Gravina and Maryam Ardalan and Tetyana Chumak and Nilsson, {Anders K.} and Ek, {Joakim C.} and Hanna Danielsson and Pernilla Svedin and Milos Pekny and Marcela Pekna and Karin S{\"a}vman and Ann Hellstr{\"o}m and Carina Mallard",

year = "2023",

month = jul,

doi = "10.1016/j.isci.2023.107217",

language = "English",

volume = "26",

journal = "iScience",

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Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants. / Gravina, Giacomo; Ardalan, Maryam; Chumak, Tetyana et al.
In: iScience, Vol. 26, No. 7, 107217, 07.2023.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

AU - Gravina, Giacomo

AU - Ardalan, Maryam

AU - Chumak, Tetyana

AU - Nilsson, Anders K.

AU - Ek, Joakim C.

AU - Danielsson, Hanna

AU - Svedin, Pernilla

AU - Pekny, Milos

AU - Pekna, Marcela

AU - Sävman, Karin

AU - Hellström, Ann

AU - Mallard, Carina

PY - 2023/7

Y1 - 2023/7

N2 - Staphylococcus (S.) epidermidis is the most common nosocomial coagulase-negative staphylococci infection in preterm infants. Clinical signs of infection are often unspecific and novel markers to complement diagnosis are needed. We investigated proteomic alterations in mouse brain after S. epidermidis infection and in preterm infant blood. We identified lipocalin-2 (LCN2) as a crucial protein associated with cerebrovascular changes and astrocyte reactivity in mice. We further proved that LCN2 protein expression was associated with endothelial cells but not astrocyte reactivity. By combining network analysis and differential expression approaches, we identified LCN2 linked to blood C-reactive protein levels in preterm infants born <28 weeks of gestation. Blood LCN2 levels were associated with similar alterations of cytokines and chemokines in both infected mice and human preterm infants with increased levels of C-reactive protein. This experimental and clinical study suggests that LCN2 may be a marker of preterm infection/inflammation associated with cerebrovascular changes and neuroinflammation.

AB - Staphylococcus (S.) epidermidis is the most common nosocomial coagulase-negative staphylococci infection in preterm infants. Clinical signs of infection are often unspecific and novel markers to complement diagnosis are needed. We investigated proteomic alterations in mouse brain after S. epidermidis infection and in preterm infant blood. We identified lipocalin-2 (LCN2) as a crucial protein associated with cerebrovascular changes and astrocyte reactivity in mice. We further proved that LCN2 protein expression was associated with endothelial cells but not astrocyte reactivity. By combining network analysis and differential expression approaches, we identified LCN2 linked to blood C-reactive protein levels in preterm infants born <28 weeks of gestation. Blood LCN2 levels were associated with similar alterations of cytokines and chemokines in both infected mice and human preterm infants with increased levels of C-reactive protein. This experimental and clinical study suggests that LCN2 may be a marker of preterm infection/inflammation associated with cerebrovascular changes and neuroinflammation.

KW - Immunology

KW - Neurology

KW - Proteomics

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AN - SCOPUS:85164995076

SN - 2589-0042

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JO - iScience

JF - iScience

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Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

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