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

Jung Eun LeeAh Rim LeeEun-Young ChoiIn Soon ChoiSung-Jo Kim
Published in: Inflammopharmacology (2023)
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.
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