Methionine sulfoximine reduces proinflammatory cytokine release by murine macrophages

• DOI: 10.1096/fasebj.31.1_supplement.615.4
• Publication Date: 2023-11-26T17:18:44Z
• Authors: Tyler Peters; Amruta Jambekar; William Brusilow
• Keywords: Proinflammatory cytokine

Methionine sulfoximine (MSO) is an amino acid that irreversibly inhibits glutamine synthetase (GS). Several studies have linked aberrant GS activity with pathological states, and inhibition by MSO has been extensively reviewed. We previously shown IP injection of (50mg/kg) increases survival decreases pro‐inflammatory cytokine levels in a mouse model acute liver failure. are trying to characterize this activity, we present evidence directly modulates the innate immune response decreasing secretion macrophages. Primary rat kupffer cells peritoneal macrophages were treated prior addition 1ug/mL LPS. A array analysis demonstrated appreciable TNFα IL‐6 supernatants from compared controls. These data confirmed ELISA quantification showing significantly reduced at both 4 hours 6 after LPS treatment cell culture models (p<0.05). currently attempting establish link between secretion, but because these used racemic mixture LS LR MSO, also purified isomer, which does not inhibit GS. Preliminary results show isomer affect response, suggesting additional target for besides synthetase.