Assessment of TNFalpha contribution to the functional up-regulation of kinin B(1) receptors in the mouse paw after treatment with LPS.
It has been widely demonstrated that LPS is able to induce kinin B(1) 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 TNFalpha in the functional up-regulation of B(1) receptors in the mouse paw. Systemic treatment with LPS (10 microg/animal, i.v. 24 h before) resulted in a marked increase (about 5-fold) in the mouse paw edema induced by the selective B(1) receptor agonist des-Arg(9)-BK (50 nmol/paw) in both Swiss and C57/BL6 mice. The up-regulation of des-Arg(9)-BK-caused edema following LPS treatment was found to be greatly diminished in TNFalpha p55(-/-) receptor knockout mice. In addition, the paw edema evoked by des-Arg(9)-BK was significantly reduced when mice received the anti-TNFalpha antibody (100 [corrected] microg/kg, i.v.) 5 min before the LPS treatment. A similar inhibition of B(1) receptor-mediated paw edema was observed when mice were treated with thalidomide (30 mg/kg, s.c.) [corrected] a drug known for reducing TNFalpha synthesis, 5 min prior to LPS administration. ELISA experiment [corrected] revealed that TNFalpha 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 TNFalpha is probably responsible for driving the sequence of events involved in the functional up-regulation of B(1) receptors in the mouse paw.
Rocha
Ana C C
AC
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, 88049-900, Florianópolis, SC, Brazil.
Fernandes
Elizabeth S
ES
Passos
Giselle F
GF
Calixto
João B
JB
Campos
Maria M
MM
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D013792:Thalidomide / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D008070:Lipopolysaccharides; D043783:Receptor, Bradykinin B1; D014409:Tumor Necrosis Factor-alpha; C024626:bradykinin, des-Arg(9)-; D013792:Thalidomide; D001920:Bradykinin