Rolipram inhibits staphylococcal enterotoxin B-mediated induction of the human skin-homing receptor on T lymphocytes.
The cutaneous lymphocyte-associated antigen defines T lymphocytes with cutaneous tropism under inflammatory conditions. Bacterial infections participate in cutaneous inflammations, such as atopic dermatitis or psoriasis. Bacterial superantigens, such as staphylococcal enterotoxin B, can activate peripheral blood mononuclear cells to induce effector T cells bearing the T cell skin homing receptor cutaneous lymphocyte-associated antigen via enhancement of interleukin-12 production. We have identified and characterized the anti-inflammatory effects of different phosphodiesterase inhibitors on this system. Our data indicate that the selective type 4 phosphodiesterase inhibitor rolipram inhibits the Staphylococcal enterotoxin B-mediated generation of cutaneous lymphocyte-associated antigen positive CD3+ cells from peripheral blood mononuclear cells by reducing interleukin-12 production in a concentration-dependent manner. Conversely, type 3 phosphodiesterase or type 5 phosphodiesterase selective inhibitors were not effective. The rolipram inhibitory effect was on interleukin-12 production, as exogenously added interleukin-12 could revert rolipram suppression. These results suggest that selective type 4 phosphodiesterase inhibition may have beneficial effects on T cell mediated skin inflammatory processes characterized by the presence of bacterial infections, that are thought to exacerbate ongoing skin inflammation.
Almirall Prodesfarma S.A. Research Center, Barcelona, Spain.
L F
LF
Santamaria
R
R
Torres
A M
AM
Giménez-Arnau
J M
JM
Giménez-Camarasa
H
H
Ryder
J M
JM
Palacios
J
J
Beleta
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D003994:Bucladesine / Q000494:pharmacology; D017252:CD3 Complex / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D020889:Rolipram; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017252:CD3 Complex; C063419:CTAGE1 protein, human; D004768:Enterotoxins; D008562:Membrane Glycoproteins; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D016201:Receptors, Lymphocyte Homing; D018664:Interleukin-12; C031818:enterotoxin B, staphylococcal; D003994:Bucladesine; D000242:Cyclic AMP; D020889:Rolipram; D015232:Dinoprostone