Batimastat reduces Mycobacterium tuberculosis-induced apoptosis in macrophages.
In this study, we report evidences that Mycobacterium tuberculosis (MTB)-induced apoptosis in macrophages is reduced by a broad-spectrum hydroxamic acid-based matrix metalloproteinase (MMP) inhibitor, Batimastat (BB-94). In particular, we show that BB-94 administration to MTB-infected macrophages inhibits apoptosis and the downmodulation of membrane CD14 expression. Moreover, the addition of broad spectrum matrix metalloproteinase inhibitor to cell culture, during MTB infection, decreases the release of soluble TNF-alpha and leads to a simultaneous increase of membrane TNF-alpha. These results show that MTB-induced apoptosis in macrophages is reduced by a MMP inhibitor and most probably is related to TNF-alpha release. This identifies BB-94 as a simultaneous anti-apoptotic and anti-inflammatory molecule during MTB infection.
Santucci
M B
MB
Department of Biology, Laboratory of Immunochemistry and Molecular Pathology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, 00133, Rome, Italy.
Ciaramella
A
A
Mattei
M
M
Sumerska
T
T
Fraziano
M
M
D017304:Annexin A5 / Q000032:analysis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011419:Propidium / Q000032:analysis / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D017304:Annexin A5; D006684:HLA-DR Antigens; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; D011419:Propidium; D010649:Phenylalanine; C080985:batimastat