Novel protein kinase C and matrix metalloproteinase inhibitors of vegetable origin as potential modulators of Langerhans cell migration following hapten-induced sensitization.
BACKGROUND
Migration and maturation of epidermal dendritic cells, the Langerhans cells (LC), are central events in the initiation of the cutaneous immune response. LC migration from skin to draining lymph nodes is regarded as an indispensable step for the early phase of antigen-specific sensitization. Among the several agents which influence the ability of LC to migrate, previous studies have revealed that matrix metalloproteinases (MMPs) and protein kinase C (PKC) contribute to promoting LC migration. In this work, we studied the effect of two recently developed PKC and MMPs inhibitors of vegetable origin on the migration of in vitro activated LC.


METHODS
The migratory capacity of epidermal and in vitro generated LC was assessed using a reconstituted basement membrane assay (Matrigel), mimicking the prerequisite passage through the dermal-epidermal basement membrane on the way to the lymph nodes.


RESULTS
Contact with chemical allergens, Bandrowski's base or 2,4-dinitrobenzenesulfonic acid (DNBS), triggered migration. In the presence of PKC inhibitors, D-erythro-sphingosine and OX100, or an inhibitor of MMPs, LU105, allergen-induced migration of LC was strongly decreased. The association between OX100 and LU105 was more efficient in modulating the migration of activated LC compared to each molecule tested separately.


CONCLUSIONS
These results showed that PKC and MMPs inhibitors act in synergy to inhibit the migration of activated epidermal dendritic cells in vitro. They underscore the role of PKC and MMPs inhibitors and suggest they may be of relevance for therapeutically regulating epidermal dendritic cell migration in inflammatory dermatoses.
Staquet
M J
MJ
INSERM 346, Lyon, France.
Piccardi
N
N
Piccirilli
A
A
Vincent
C
C
Schmitt
D
D
Msika
P
P
D015703:Antigens, CD / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology; D051940:B7-2 Antigen; D001557:Benzenesulfonates / Q000276:immunology; D002464:Cell Migration Inhibition; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000276:immunology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D031297:Lupinus; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010655:Phenylenediamines / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000276:immunology; D013110:Sphingosine / Q000494:pharmacology*
D015703:Antigens, CD; D018949:Antigens, CD1; D051940:B7-2 Antigen; D001557:Benzenesulfonates; C419393:CD1a antigen; C497964:CD86 protein, human; D004791:Enzyme Inhibitors; C481500:Lupinus albus extract 105; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D010080:Oxazoles; D010655:Phenylenediamines; D010936:Plant Extracts; C051597:Bandrowski's base; C001073:2,4-dinitrobenzenesulfonic acid; D011493:Protein Kinase C; D020782:Matrix Metalloproteinases; D013110:Sphingosine