Corynebacterium parvum- and Mycobacterium bovis bacillus Calmette-Guerin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI) knockout mice and by treatment with soluble TNF-RI.
The aim of this study was to examine the role of TNF receptor I (TNF-RI) in the pathogenesis of heat-killed Corynebacterium parvum- and live bacillus Calmette-Guerin (BCG)-induced granulomas. Granuloma formation was analyzed in TNF-RI knockout mice and after treatment with soluble TNF-RI (sTNF-RI). TNF-RI knockout mice injected with C. parvum or BCG developed fewer and smaller granulomas than wild-type control mice. Mice treated with sTNF-RI from days 7 to 13 after injection of C. parvum or BCG developed fewer and smaller granulomas than saline-treated control mice. Established granulomas regressed in rats treated with sTNF-RI from days 10 to 13 after injection of C. parvum. In conclusion, TNF signaling via TNF-RI contributes to the pathogenesis of C. parvum- and BCG-induced granulomas. sTNF-RI inhibits the development of granulomas and can cause the regression of established granulomas.
Senaldi
G
G
Amgen, Inc., Thousand Oaks, CA 91320.
Yin
S
S
Shaklee
C L
CL
Piguet
P F
PF
Mak
T W
TW
Ulich
T R
TR
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D011425:Propionibacterium acnes / Q000472:pathogenicity*; D011487:Protein Conformation; D051381:Rats; D011917:Rats, Inbred Lew; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D012995:Solubility; D013158:Splenic Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins