Regulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with ciclosporin on the homeostasis of human lymphocytes
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Regulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with ciclosporin on the homeostasis of human lymphocytes. / Lee, Cheuk Lun; Jiang, Pingping; Sit, Wai Hung; Yang, Xiatong; Wan, Jennifer Man Fan.
I: Journal of Pharmacy and Pharmacology, Bind 62, Nr. 8, 08.2010, s. 1028-1036.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Regulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with ciclosporin on the homeostasis of human lymphocytes
AU - Lee, Cheuk Lun
AU - Jiang, Pingping
AU - Sit, Wai Hung
AU - Yang, Xiatong
AU - Wan, Jennifer Man Fan
PY - 2010/8
Y1 - 2010/8
N2 - Objectives Lymphocyte homoeostasis is essential in inflammatory and autoimmune diseases. In search of natural fungal metabolites with effects on lymphocyte homoeostasis, we recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin-like activity in controlling aberrant lymphocyte activation. This object of this study was to investigate its effect on lymphocyte homoeostasis. This was done by investigating the mechanistic actions of PSP in relation to ciclosporin by performing cell cycle and cell death analysis of human lymphocytes in vitro. Methods We investigated the effect of PSP in the presence and absence of ciclosporin on cell proliferation, cell cycle, cell death, immunophenotype and cell cycle regulatory proteins in human lymphocytes. Key findings The data showed that PSP exhibited homoeostatic activity by promoting and inhibiting the proliferation of resting and phytohaemagglutinin (PHA)-stimulated lymphocytes, respectively. PHA-stimulated lymphocytes exhibited G0/G1 cell cycle arrest that was accompanied by a reduction of cyclin E expression with PSP treatment. Both PSP and ciclosporin blocked the reduction of the CD4/CD8 ratio in stimulated lymphocytes. PSP did not induce cell death in human lymphocytes, but the suppression of the Fasreceptor suggested a protective role of PSP against extrinsic cell death signals. These homoeostatic effects were more potent with combined PSP and ciclosporin treatment than with either fungal metabolite alone. Conclusions Collectively, the results reveal certain novel effects of PSP in lymphocyte homoeostasis and suggest potential as a specific immunomodulatory adjuvant for clinical applications in the treatment of autoimmune diseases.
AB - Objectives Lymphocyte homoeostasis is essential in inflammatory and autoimmune diseases. In search of natural fungal metabolites with effects on lymphocyte homoeostasis, we recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin-like activity in controlling aberrant lymphocyte activation. This object of this study was to investigate its effect on lymphocyte homoeostasis. This was done by investigating the mechanistic actions of PSP in relation to ciclosporin by performing cell cycle and cell death analysis of human lymphocytes in vitro. Methods We investigated the effect of PSP in the presence and absence of ciclosporin on cell proliferation, cell cycle, cell death, immunophenotype and cell cycle regulatory proteins in human lymphocytes. Key findings The data showed that PSP exhibited homoeostatic activity by promoting and inhibiting the proliferation of resting and phytohaemagglutinin (PHA)-stimulated lymphocytes, respectively. PHA-stimulated lymphocytes exhibited G0/G1 cell cycle arrest that was accompanied by a reduction of cyclin E expression with PSP treatment. Both PSP and ciclosporin blocked the reduction of the CD4/CD8 ratio in stimulated lymphocytes. PSP did not induce cell death in human lymphocytes, but the suppression of the Fasreceptor suggested a protective role of PSP against extrinsic cell death signals. These homoeostatic effects were more potent with combined PSP and ciclosporin treatment than with either fungal metabolite alone. Conclusions Collectively, the results reveal certain novel effects of PSP in lymphocyte homoeostasis and suggest potential as a specific immunomodulatory adjuvant for clinical applications in the treatment of autoimmune diseases.
KW - ciclosporin
KW - Coriolus versicolor
KW - lymphocyte
KW - polysaccharopeptide
KW - proteoglycan
UR - http://www.scopus.com/inward/record.url?scp=77954939161&partnerID=8YFLogxK
U2 - 10.1211/jpp.62.08.0009
DO - 10.1211/jpp.62.08.0009
M3 - Journal article
C2 - 20663037
AN - SCOPUS:77954939161
VL - 62
SP - 1028
EP - 1036
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 8
ER -
ID: 299106251