Aspirin downregulates homocysteine formation in stimulated human peripheral blood mononuclear cells.
Moderate hyperhomocysteinaemia is established as an independent risk factor for atherosclerosis, thrombosis, stroke and dementia. Hyperhomocysteinaemia is mostly caused by the deficiency of B-vitamins folate and vitamin B12, which are essential cofactors in the remethylation of homocysteine to methionine. Interestingly, moderate hyperhomocysteinaemia is also often observed in chronic diseases, in which also elevated immune activation markers such as neopterin or sTNFR-II are found. In order to simulate immune activation in vitro, human peripheral blood mononuclear cells (PBMC) were stimulated with mitogens. Stimulation significantly increased homocysteine production in comparison with unstimulated PBMC; in parallel also neopterin formation was induced. Homocysteine formation was due to cell proliferation, proliferating T lymphocytes, and also the myelomonocytic cell line U-937 produced homocysteine. Treatment with the anti-inflammatory drug aspirin dose-dependently inhibited homocysteine production and also neopterin formation in human PBMC. Treatment with salicylic acid showed similar effects as aspirin; FACS analysis showed that both compounds inhibited cell proliferation by arresting cells in the G0/G1-phase. In U-937, both compounds also slightly induced apoptosis at 5 mm. Proliferation-induced homocysteine formation and in parallel also monocyte activation can be suppressed effectively by aspirin and salicylic acid in vitro, suggesting that also in vivo aspirin may downregulate not only inflammation but also formation of homocysteine.
Schroecksnadel
K
K
Department of Biological Chemistry, Biocentre, Innsbruck Medical University, A-6020 Innsbruck, Austria.
Frick
B
B
Winkler
C
C
Wirleitner
B
B
Schennach
H
H
Fuchs
D
D
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D003208:Concanavalin A / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D006710:Homocysteine / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D019798:Neopterin / Q000032:analysis; D010835:Phytohemagglutinins / Q000276:immunology; D011043:Pokeweed Mitogens / Q000276:immunology; D020298:U937 Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D006710:Homocysteine; D003208:Concanavalin A; D019798:Neopterin; D001241:Aspirin