Anti-inflammatory Effects of Phosphatidylcholine

Abstract

We recently showed that mucus from patients with ulcerative colitis, a chronic inflammatory disorder of the colon, is characterized by a low level of phosphatidylcholine (PC) while clinical studies reveal that therapeutic addition of PC using slow release preparations is beneficial. The positive role of PC in this disease is still elusive. Here we tested the hypothesis that exogenous application of PC has anti-inflammatory properties using three model systems. First, human Caco-2 cells were treated with tumor necrosis factor-␣ (TNF-␣) to induce a pro-inflammatory response via activation of NF-B. Second, latex bead phagosomes were analyzed for their ability to assemble actin in vitro, a process linked to pro-inflammatory signaling and correlating with the growth versus killing of mycobacteria in macrophages. The third system used was the rapid assembly of plasma membrane actin in macrophages in response to sphingosine 1-phosphate. TNF-␣ induced a pro-inflammatory response in Caco-2 cells, including 1) assembly of plasma membrane actin; 2) activation of both MAPKs ERK and p38; 3) transport of NF-B subunits to the nucleus; and 4) subsequent up-regulation of the synthesis of pro-inflammatory gene products. Exogenous addition of most PCs tested significantly inhibited these processes. Other phospholipids like sphingomyelin or phosphatidylethanolamine showed no effects in these assays. PC also inhibited latex bead phagosome actin assembly, the killing of Mycobacterium tuberculosis in macrophages, and the sphingosine 1-phosphate-induced actin assembly in macrophages. TNF-␣ induces the activation of signaling molecules and the reorganization of the actin cytoskeleton in human intestinal cells. Exogenous application of PC blocks pro-inflammatory signaling in Caco-2 cells, in phagosomes in vitro and facilitates intracellular survival of mycobacteria. We provide further evidence that actin assembly by membranes is part of the pro-inflammatory response. Collectively, these results provide a molecular foundation for the clinical studies showing a beneficial effect of PC therapy in ulcerative colitis.

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

“…Reduction in the content of PC aa in the gastrointestinal mucosae leads to increased invasion of pathogens (118). PC aa derivatives in the plasma membrane inhibit actin polymerization, inhibit phagosomal actin assembly, stimulate Mycobacterium survival in phagosomes, and increase nitric oxide production (78,118,119). These PC aa functions are also complementary with the proposed increase in actin rearrangements suggested by the proteomics analysis (Fig.…”

“…7). In other systems, these molecules play important roles in mucous production, actin polymerization, and host signaling (77)(78)(79)(80).…”

Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation Into Cancer and Nutrition–Potsdam Study

“…[35][36][37][38] It was shown that phosphatidylcholines are able to inhibit the upregulation of the inflammatory cytokines tumor necrosis factor-α and interleukin-6 and the actin-assembly in phagosomes and macrophages. 35,37 Moreover, phosphatidylcholines seem to be required for lipoprotein assembly and hepatic secretion of triglyceride-rich very low-density lipoprotein particles as well as high-density lipoprotein particles.39 Through a vinyl-ether bond in the acyl-alkyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines may be capable to act as blood antioxidants to protect lipoproteins from oxidation. 40 Moreover, in a previous study, it was shown that acylalkyl-phosphatidylcholines were positively correlated with high-density lipoprotein-cholesterol.…”

“…In this context, it is interesting to note that recent studies have assigned a possibly anti-inflammatory role under different conditions (eg, oxidative stress and ulcerative colitis) to phosphatidylcholines. [35][36][37][38] It was shown that phosphatidylcholines are able to inhibit the upregulation of the inflammatory cytokines tumor necrosis factor-α and interleukin-6 and the actin-assembly in phagosomes and macrophages. 35,37 Moreover, phosphatidylcholines seem to be required for lipoprotein assembly and hepatic secretion of triglyceride-rich very low-density lipoprotein particles as well as high-density lipoprotein particles.…”

Lack of Effect of Choline Supplement on Inflammation, Muscle Endurance and Injury Indices, and Shooting Accuracy Following Simulated Army Ranger Operation

“…A previous study by the authors showed that choline supplementation could improve endurance performance and metabolic fatigue in elite cyclists during 2 hours of laboratory cycling tests (15). Choline could also induce anti-inflammatory effects, since inflammatory indices (C-reactive protein, homocysteine, interleukin-6, and tumor necrosis factor) were found to be lower in subjects with choline rich diets (16). Animal studies suggest that sleep deprivation decreases cholinecontaining compounds in the brain and this may explain the cognitive and mental concentration impairments in sleep deprived subjects (17).…”