Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9008162 | International Immunopharmacology | 2005 | 8 Pages |
Abstract
It has been widely demonstrated that LPS is able to induce kinin B1 receptor up-regulation throughout several models of inflammation. Using an in-vivo system in which LPS was administered systemically, we assessed the participation of the pro-inflammatory cytokine TNFα in the functional up-regulation of B1 receptors in the mouse paw. Systemic treatment with LPS (10 μg/animal, i.v. 24 h before) resulted in a marked increase (about 5-fold) in the mouse paw edema induced by the selective B1 receptor agonist des-Arg9-BK (50 nmol/paw) in both Swiss and C57/BL6 mice. The up-regulation of des-Arg9-BK-caused edema following LPS treatment was found to be greatly diminished in TNFα p55â/â receptor knockout mice. In addition, the paw edema evoked by des-Arg9-BK was significantly reduced when mice received the anti-TNFα antibody (500 μg/kg, i.v.) 5 min before the LPS treatment. A similar inhibition of B1 receptor-mediated paw edema was observed when mice were treated with thalidomide (30 mg/kg, s.c), a drug known for reducing TNFα synthesis, 5 min prior to LPS administration. ELISA experiments revealed that TNFα serum levels were maximal at 1 h following LPS systemic treatment. Taken together, the present results suggest that the early production of the pro-inflammatory cytokine TNFα is probably responsible for driving the sequence of events involved in the functional up-regulation of B1 receptors in the mouse paw.
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Authors
Ana C.C. Rocha, Elizabeth S. Fernandes, Giselle F. Passos, João B. Calixto, Maria M. Campos,