You are here: Home :: Area NEM :: Life sciences :: Biochemistry

Renata M??yk-Kope?, Ma?gorzata Bzowska, Monika Bzowska, Barbara Mickowska, Pawe? Mak, Jan Potempa, Joanna Bereta

Effects of elastase and cathepsin G on the levels of membrane and soluble TNF?

Keywords: cathepsin G, elastase, inflammation, neutrophil, shedding, tumor necrosis factor ? (TNF?)

Neutrophil elastase (NE) and cathepsin G (CG), the proteolytic enzymes localized in azurophil granules of neutrophils (PMN), are involved in PMN responses to various stimuli. When released at sites of inflammation, they participate in the degradation of numerous proteins involved in the regulation of the immune response. In this study, we employed ADAM17^-/- fibroblasts stably transfected with cDNA of human pro-tumor necrosis factor ? (proTNF?) (ADAM17^-/-TNF⁺) to investigate the effects of NE and CG on shedding and degradation of TNF?. Both NE and CG were found to diminish the level of membrane TNF? (mTNF?) as measured by flow cytometry. This process was accompanied by the accumulation of biologically active soluble TNF? (sTNF?) in the culture medium, as determined by an increase in both the cytotoxic activity of TNF? and its ability to serve as a co-stimulator in the induction of inducible nitric oxide synthase (iNOS). However, in contrast to CG, NE at high concentrations was able to degrade sTNF? released from the cell surface. Using soluble recombinant human TNF?, we identified Val⁹³-Ala⁹⁴ and Val¹¹⁷-Glu¹¹⁸ as the NE cleavage sites within the sTNF? molecule. Taken together, the ability of NE and CG to modulate levels of membrane and soluble forms of TNF? may contribute to the proinflammatory activity of neutrophils.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 386, 08/2005
Pages: 801 - 811

Show full article (external site)

Show all available items of this journal

 

Area NEM