Cynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98 functions.
Cynaropicrin is a sesquiterpene lactone displaying immunomodulatory effects on the production of cytokine and nitric oxide from macrophages/monocytes. In this study we have examined inhibitory effect of cynaropicrin on activation of major adhesion molecules [CD29 (beta1 integrins), CD43, and CD98] on the cells assessed by U937 (promonocytic cells) homotypic aggregation. Cynaropicrin potently blocked CD29 (beta1 integrins)- and CD98-induced homotypic aggregation with IC(50) values of 3.46 and 2.98 microM, respectively, without displaying cytotoxicity. Similarly, flow cytometric analysis exhibited that cynaropicrin down-regulated strikingly surface level of CD29 and CD147, a functional regulator of CD98, but not CD43. More importantly, cynaropicrin inhibition was linked to blockade of extracellular signal-related kinase (ERK) activation and distinct from other enzyme inhibitors including rottlerin, propranolol, forskolin, and chloroquine, but not cytochalasin B. Therefore, our finding is the first demonstration that cynaropicrin may be a potent functional regulator of CD29 and CD98 via interrupting ERK activation which may be linked to cytoskeleton rearrangement, suggesting further application to CD29- and CD98-mediated diseases such as virus-induced chronic inflammation, and invasion, migration, and metastasis of leukocyte cancer cells.
Cho
Jae Youl
JY
School of Biotechnology and Bioengineering, Kangwon National University, Chuncheon 200-701, Republic of Korea. jaecho@kangwon.ac.kr
Kim
Ae Ra
AR
Joo
Hong-Gu
HG
Kim
Byung-hun
BH
Rhee
Man Hee
MH
Yoo
Eun Sook
ES
Katz
David R
DR
Chain
Benjamin M
BM
Jung
Jee H
JH
D015703:Antigens, CD; D002449:Cell Aggregation / Q000187:drug effects; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D051917:Leukosialin; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells
D015703:Antigens, CD; D027261:Fusion Regulatory Protein-1; D019012:Integrin beta1; D007783:Lactones; D051917:Leukosialin; C465014:SPN protein, human; D012717:Sesquiterpenes; D012795:Sialoglycoproteins; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases; C075687:cynaropicrin