Effect of nitro-conjugated linoleic acid on the inflammatory response of murine macrophages activated with lipopolysaccharide derived from Prevotella intermedia.

Nitro-conjugated linoleic acid (NO ₂ -CLA) has been observed to manifest salutary signaling responses, including anti-inflammatory and antioxidant properties. Here, the authors have explored the influence and underlying mechanisms of NO ₂ -CLA on the proinflammatory reaction of murine macrophages that were challenged with lipopolysaccharide (LPS) derived from Prevotella intermedia, a putative periodontopathic bacterium. Treatment of LPS-activated RAW264.7 cells with NO ₂ -CLA notably dampened the secretion of iNOS-derived NO, IL-1β and IL-6 as well as their gene expressions and significantly enhanced the markers for M2 macrophage polarization. NO ₂ -CLA promoted the HO-1 expression in cells challenged with LPS, and tin protoporphyrin IX, an HO-1 inhibitor, significantly reversed the NO ₂ -CLA-mediated attenuation of NO secretion, but not IL-1β or IL-6. We found that cells treated with NO ₂ -CLA significantly increased mRNA expression of PPAR-γ compared to control cells, and NO ₂ -CLA significantly reverted the decrease in PPAR-γ mRNA caused by LPS. Nonetheless, antagonists to PPAR-γ were unable to reverse the NO ₂ -CLA-mediated suppression of inflammatory mediators. In addition, NO ₂ -CLA did not alter the p38 and JNK activation elicited by LPS. Both NF-κB reporter activity and IκB-α degradation caused by LPS were notably diminished by NO ₂ -CLA. NO ₂ -CLA was observed to interrupt the nuclear translocation and DNA binding of p50 subunits caused by LPS with no obvious alterations in p65 subunits. Further, NO ₂ -CLA attenuated the phosphorylation of STAT1/3 elicited in response to LPS. We propose that NO ₂ -CLA could be considered as a possible strategy for the therapy of periodontal disease, although additional researches are certainly required to confirm this.
(© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)