In early-stage
sepsis,
glucose metabolism is increased primarily through glycolysis in the inflammatory response of M1 macrophages.
Heparin-binding protein (HBP) has been linked to
sepsis, which can promote macrophage activation and inflammatory factor release. However, the mechanism by which
glucose metabolism regulates the inflammatory response is unclear. We show that HBP contributes to
sepsis by modulating the inflammatory response via
lactate-dependent glycolysis in macrophages. Peritoneal macrophages from BALB/c mouse were treated with
lipopolysaccharide (LPS). The expression of M1-related proinflammatory genes was investigated by PCR array. IL-1β, iNOS, TNF-α, and
IL-6 mRNA expression was determined by qRT-PCR. Intracellular
lactate levels were measured using
lactate assays.
Nuclear factor-kappaB (NF-κB) activity was determined by electrophoretic mobility shift assays (EMSAs). TNF-α levels were measured by qRT-PCR. HBP enhanced inflammatory gene expression in mouse peritoneal macrophages and intracellular
lactate accumulation and significantly increased LPS-stimulated NF-κB transcriptional activity and TNF-α expression through
lactate.
Lactate was essential for the HBP-induced increase in LPS-stimulated TNF-α expression. The critical role of
lactate in HBP-induced NF-κB signaling was confirmed, as α-CHCA-mediated (MCT) suppression significantly inhibited NF-κB activity and TNF-α expression. HBP plays an important role in the initial inflammatory reaction, presumably by activating M1 macrophages, increasing
lactate levels, and regulating proinflammatory factor release via NF-κB pathway activation.