学術データベース

A specific phosphodiesterase 4 inhibitor, rolipram, downregulates mite antigen-induced expression of interleukin-5 mRNA in human peripheral blood mononuclear cells.

著者名

田渕　正樹 (Tabuchi Masaki)

共著者名

Markova TP, Niwa A, Aragane Y, Higashino H.

出版社／掲載誌名

Acta. Med. Kinki Univ.

巻号

35(3/4)

頁

97-102

出版日

2010/12

概要

It is known that agents leading to the elevation of cellular adenosine 3',5'-cyclic monophosphate (cAMP) levels may have the potential to prevent the activation of cellular events. Among a panel of phosphodiesterase (PDE) enzymes, PDE4 is preferentially expressed in immune cells, which catalyze the breakdown of cellular cAMP and thus may have potent immunomodulatory activities. Here we studied whether rolipram, a specific PDE4 inhibitor, may regulate immune responses. Peripheral blood mononuclear cells were isolated from human healthy volunteers and cultured in the presence or absence of mite antigen, dermatophagoides farinae (Der-f), which is known to be pathogenically causative of atopic disorders. Cells were further treated with graded concentrations of rolipram or left untreated. Eighteen hours later, cells were harvested, RNA extracted, and finally semi-quantitative RT-PCR was conducted using primers for IL-5. It was found that stimulation with Der-f led to the upregulation of interleukin (IL)-5 mRNA. Rolipram significantly downregulated Der-f-upregulated expression of IL-5 mRNA, which also occurred with a cAMP analogue, 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP). It is known that elevated cellular cAMP levels lead to the activation of protein kinase A (PKA) pathways, which might be capable of, at least in part, deactivation of cellular events. Therefore, we hypothesized that inhibition of PKA activity might restore rolipram-downregulation of the IL-5 mRNA expression if PKA activation plays a role in this event, however, it was not affected by a PKA inhibitor, 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Br-cAMPS). Our study indicates that rolipram definitely downregulates mite antigen-induced activation of peripheral immunocompetent cells, and suggests that this phenomenon is not directly dependent on PKA activation.