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Inhibition of mitogenic stimulant-induced activation of thymocytes with zinc tetrakis-(N-methyl-4′-pyridyl) porphyrinato

Title
Inhibition of mitogenic stimulant-induced activation of thymocytes with zinc tetrakis-(N-methyl-4′-pyridyl) porphyrinato
Authors
Kang J.L.Lee H.S.Jung H.J.Kim H.J.Hah J.S.Castranova V.
Ewha Authors
이지희
SCOPUS Author ID
이지희scopus
Issue Date
2002
Journal Title
Journal of Pharmacology and Experimental Therapeutics
ISSN
0022-3565JCR Link
Citation
vol. 303, no. 3, pp. 1138 - 1144
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Zinc porphyrins have anti-inflammatory and anti-allergic properties. The objective of the present study was to characterize the mechanism of zinc tetrakis-(N-methyl-4′-pyridyl) porphyrinato (ZnTMPyP) immune modulation by investigating its effects on the proliferative activity during thymocyte stimulation with mitogenic factors and the molecular events mediating thymocyte proliferation. The results indicate that ZnTMPyP inhibited thymocyte proliferation stimulated with various mitogenic factors, such as concanavalin A (Con A), interleukin (IL)-1/β, and lipopolysaccharide-exposed macrophage supernatant, in a concentration-dependent manner. ZnTMPyP was also effective in preventing DNA binding activity of nuclear factor κB (NF-κB) and IL-2 production by thymocytes in response to Con A or IL-1β. Inhibition of p38 mitogen-activated protein kinase (MAPK) with SB203580 substantially inhibited Con A- or IL-1β-induced DNA binding activity of NF-κB, whereas ZnTMPyP inhibited the activation of p38 MAPK. ZnTMPyP also inhibited Con A-induced chemiluminescence and tyrosine phosphorylation by thymocytes. In conclusion, our findings suggest that the antiproliferative effect of ZnTMPyP may be mediated by effective inhibition of the production of reactive oxygen species, tyrosine phosphorylation, p38 MAPK activation, NF-κB activation, and IL-2 production during mitogenic stimulation of thymocytes.
DOI
10.1124/jpet.102.039123
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의학전문대학원 > 의학과 > Journal papers
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