Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect 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 (10ng/mL) and TNFα (100ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-α. Supernatants were collected 24 h after treatment and analysed for 23 inflammatory mediators including pro- and anti-inflammatory cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and IGF-1. Phosphorylation of proteins (AKT, ERK1/2, IB-α, 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-α 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-α induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-α-induced microglia response for cytokines, chemokines and phosphorylation of IB-α. 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 the TLR4 receptor. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation suggesting a potential protective effect in infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge.