Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions
Artikel i vetenskaplig tidskrift, 2021

Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation. Thus, we investigated the effect of galectin-3 on microglia in vitro under normal as well as infectious and sterile inflammatory conditions, and the effect of galectin-3 on neonatal brain injury following an infectious challenge in vivo. Conditions mimicking infectious or sterile inflammation were evaluated in primary microglia cell cultures from newborn mice, using LPS (10 ng/mL) and TNF-alpha (100 ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-alpha. Supernatants were collected 24 h after treatment and analyzed for 23 inflammatory mediators including pro- and anti-inflammatory cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and insulin-like growth factor (IGF)-1. Phosphorylation of proteins (AKT, ERK1/2, I kappa B-alpha, JNK, and p38) was determined in microglia cells. Neonatal brain injury was induced by a combination of LPS and HI (LPS + HI) in postnatal day 9 transgenic mice lacking functional galectin-3 and wild-type controls. LPS and TNF-alpha induced pro-inflammatory (9/11 vs. 9/10) and anti-inflammatory (6/6 vs. 2/6) cytokines, as well as chemokines (6/6 vs. 4/6) in a similar manner, except generally lower amplitude of the TNF-alpha-induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-alpha-induced microglia response for cytokines, chemokines, and phosphorylation of I kappa B-alpha. LPS decreased baseline IGF-1 levels, and the levels were restored by galectin-3. Brain injury or microglia response after LPS + HI was not affected by galectin-3 deficiency. Galectin-3 has no independent effect on microglia but modulates inflammatory activation in vitro. The effect was similar under infectious and sterile inflammatory conditions, suggesting that galectin-3 regulates inflammation not just by binding to LPS or toll-like receptor-4. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation, suggesting a potential protective effect on infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge.

Insulin-like growth factor




Brain injury



Karin Savman

Göteborgs universitet

Wei Wang

Göteborgs universitet

Ali Hoseinpoor Rafati

Göteborgs universitet

Pernilla Svedin

Göteborgs universitet

Syam Nair

Göteborgs universitet

Veronika Golubinskaya

Göteborgs universitet

Maryam Ardalan

Göteborgs universitet

Kelly L. Brown

British Columbia Children's Hospital

University of British Columbia (UBC)

Anna Karlsson-Bengtsson

Chalmers, Biologi och bioteknik, Kemisk biologi

Göteborgs universitet

Carina Mallard

Göteborgs universitet

Developmental Neuroscience

0378-5866 (ISSN) 1421-9859 (eISSN)

Vol. 43 5 296-311

Glykosylering i humana neutrofiler vid sepsis och systemisk inflammation

Vetenskapsrådet (VR) (2018-03077), 2019-01-01 -- 2024-12-31.





Immunologi inom det medicinska området

Farmakologi och toxikologi





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