Suberosin inhibits proliferation of human peripheral blood mononuclear cells through the modulation of the transcription factors NF-AT and NF-kappaB.

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0007-1188 (Print) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

Plumbaginaceae*; Anti-Inflammatory Agents/*pharmacology ; Cell Cycle/*drug effects ; Cell Proliferation/*drug effects ; Coumarins/*pharmacology ; NF-kappa B/*drug effects ; NFATC Transcription Factors/*drug effects; Gene Expression ; Humans ; In Vitro Techniques ; Leukocytes, Mononuclear/drug effects ; NF-kappa B/physiology ; NFATC Transcription Factors/physiology ; Plant Extracts ; Polymerase Chain Reaction

Background and Purpose: Extracts of Plumbago zeylanica containing suberosin exhibit anti-inflammatory activity. We purified suberosin from such extracts and studied its effects on a set of key regulatory events in the proliferation of human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (PHA).
Experimental Approach: Proliferation of PBMC in culture was measured by uptake of 3H-thymidine; production of cytokines and cyclins by Western blotting and RT-PCR. Transcription factors NF-AT and NF-kappaB were assayed by immunocytochemistry and EMSA.
Key Results: Suberosin suppressed PHA-induced PBMC proliferation and arrested cell cycle progression from the G1 transition to the S phase. Suberosin suppressed, in activated PBMC, transcripts of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and cyclins D3, E, A, and B. DNA binding activity and nuclear translocation of NF-AT and NF-kappaB induced by PHA were blocked by suberosin. Suberosin decreased the rise in intracellular Ca2+ concentration ([Ca2+]i) in PBMC stimulated with PHA. Suberosin did not affect phosphorylation of p38 and JNK but did reduce activation of ERK in PHA-treated PBMC. Pharmacological inhibitors of NF-kappaB, NF-AT, and ERK decreased expression of mRNA for the cyclins, IL-2, and IFN-gamma and cell proliferation in PBMC activated by PHA.
Conclusions and Implications: The inhibitory effects of suberosin on PHA-induced PBMC proliferation, were mediated, at least in part, through reduction of [Ca2+]i, ERK, NF-AT, and NF-kappaB activation, and early gene expression in PBMC including cyclins and cytokines, and arrest of cell cycle progression in the cells. Our observations provide an explanation for the anti-inflammatory activity of P. zeylanica.

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0 (Anti-Inflammatory Agents)
0 (Coumarins)
0 (NF-kappa B)
0 (NFATC Transcription Factors)
0 (Plant Extracts)
0 (suberosin)

Date Created: 20061221 Date Completed: 20070424 Latest Revision: 20240414

20240414

PMC2013892

10.1038/sj.bjp.0706987

17179947