title: Anti-inflammatory effect of 1-methylnicotinamide in contact hypersensitivity to oxazolone in mice; involvement of prostacyclin.
abstract: 1-methylnicotinamide (MNA) displays anti-inflammatory effects in patients with contact dermatitis, though the mechanisms involved remain unknown. Herein, we examined the anti-inflammatory effects of MNA and its parent molecule, nicotinamide, in the contact hypersensitivity reaction to oxazolone in CBA/J inbred mice. Feeding mice with MNA or nicotinamide (100 mg/kg, 10 days) resulted in the inhibition of the development of contact hypersensitivity reaction by 37% and 35%, respectively, as assessed by the magnitude of ear swelling. This effect was not associated with changes in the expression of adhesion molecules (CD49d(+) and CD54(+)) on CD4(+) and CD8(+) oxazolone-specific T lymphocytes, the major cell component of an inflammatory infiltrate in contact hypersensitivity reaction. Furthermore, in the adoptive transfer model of contact hypersensitivity reaction, pretreatment of mice (recipients of oxazolone-specific T cells), with MNA, resulted in a remarkable anti-inflammatory effect (inhibition of contact hypersensitivity reaction by 66%). Interestingly, in the presence of prostanoid IP receptor antagonist R-3-(4-fluoro-phenyl)-2-[5-(4-fluoro-phenyl)-benzofuran-2-ylmethoxycarbonylamino]-propionic acid (RO-3244794) (10 mg/kg) the MNA was inactive. In summary, pretreatment with MNA profoundly attenuated contact hypersensitivity reaction in vivo. In particular, the vessel dependent phase of contact hypersensitivity reaction was affected, in spite of the fact that MNA did not alter the expression of adhesive molecules on oxazolone-specific T lymphocytes. However, the anti-inflammatory action of MNA was completely reversed by the antagonist of prostanoid IP receptor. Accordingly, our results demonstrate for the first time that anti-inflammatory properties of MNA are linked to endothelial, PGI(2)-mediated mechanisms.
authors.affiliation: Department of Immunology Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bryniarski
authors.forename: Rafal
authors.initials: R
authors.lastname: Biedron
authors.forename: Andrzej
authors.initials: A
authors.lastname: Jakubowski
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
authors.forename: Janusz
authors.initials: J
authors.lastname: Marcinkiewicz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001572:Benzofurans / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003879:Dermatologic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D039441:Integrin alpha4 / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010081:Oxazolone; D011422:Propionates / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D003879:Dermatologic Agents; D011422:Propionates; C491910:Ptgir protein, mouse; C515593:RO3244794; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4; D010081:Oxazolone; D009536:Niacinamide; D011464:Epoprostenol; C024058:N(1)-methylnicotinamide