Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Suppress Proliferation and Motility of Human [CD4.sup.+] T Lymphocytes in Culture

• Published in: Bulletin of experimental biology and medicine Vol. 172; no. 2; p. 137
• Main Authors: Radyukhina, N.V, Ruleva, N.Yu, Filatova, A.Yu, Aref'eva, T.I
• Format: Journal Article
• Language: English
• Published: Springer 01.12.2021
• Subjects: Statins; T cells; Thiols
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-021-05350-w

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) along with their blood lipid-lowering effect exhibit anti-inflammatory and immunomodulatory activity. We studied the effects of long-term (72-h or longer) exposure of human T lymphocytes in culture to atorvastatin and rosuvastatin (5-80 nM) on their functional activity. Treatment with statins inhibited PHA/IL-2-induced proliferation of [CD4.sup.+] T lymphocytes isolated from the peripheral blood of healthy donors. This was accompanied by a decrease in the relative content of cells expressing active caspase-3. Addition of mevalonate or fetal bovine serum simultaneously with statins restored proliferative activity of cells. Culturing of [CD4.sup.+] T lymphocytes with statins in the presence of IL-2 did not significantly affect the expression of chemokine receptors CCR4, CCR5, CXCR3, and CXCR4. Pretreatment with statins suppressed spontaneous and SDF-1-stimulated migration of [CD4.sup.+] T lymphocytes, but little changed the content of intracellular phosphorylated protein kinases Akt, p38 and p42/44 (ERK1/2). The cellular effects of "lipophilic" atorvastatin were observed at lower concentrations compared to "hydrophilic" rosuvastatin. Key Words: inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins); T lymphocytes; proliferation; migration; apoptosis