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Role of mitogen‐activated protein kinases in the differential regulation of interleukin‐2 by cannabinol
Author(s) -
Jan TongRong,
Kaminski Norbert E.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.5.841
Subject(s) - biology , mapk/erk pathway , cannabinol , secretion , mitogen activated protein kinase , microbiology and biotechnology , protein kinase a , kinase , endocrinology , biochemistry , receptor , cannabinoid
Cannabinoids can paradoxically regulate interleukin‐2 (IL‐2) expressioneither positively or negatively. This study investigated the mechanismresponsible for cannabinol‐mediated IL‐2 modulation. In primary murinesplenocytes and EL4.IL‐2 T cells, the contrasting effects of cannabinolon IL‐2 secretion depended on the magnitude but not the mode of T‐cellactivation. Suboptimal activation of T cells in the presence ofcannabinol produced an enhancement of IL‐2 secretion, which wasparalleled by an increase in nuclear phospho‐extracellular‐regulatedkinase (ERK) 1/2. In contrast, T cells activated with stimulithat were optimized to induce maximal IL‐2 secretion elicited a markedsuppression in the production of this cytokine when cultured in thepresence of cannabinol. Moreover, cannabinol‐mediated enhancement of IL‐2 secretion by splenocytes was attenuated to various degrees bystaurosporine, Ro‐31‐8220, and KN93. These results suggest that theenhancement of IL‐2 secretion by cannabinol is associated with anincrease in ERK mitogen‐activated protein kinase, which is proteinkinase C and calmodulin‐kinase dependent.