Role of Secretory leukocyte proteinase inhibitor (SLPI) in Mycobacterium tuberculosis infection.

TATEOSIAN N; COSTA M; PASQUINELI V; GOMEZ S; MAFFIA P; GARCÍA VE; CHULUYAN HE

Rio de Janeiro

Congreso; 13º International Congress of Immunology 2007; 2007

IUIS

Secretory leukocyte proteinase inhibitor (SLPI), a protease inhibitor purified from different sources like lung secretions, displays multiple roles during inflammatory responses.  For example, SLPI inhibits leucocyte-derived proteases and exerts antimicrobial activity.  However, the role of SLPI during mycobacterial infection has not been reported.  Thus, we investigated the function of SLPI against Mycobacterium tuberculosis (MTB).  We then examinated whether MTB antigen could modulate SLPI levels secreted from  peripheral blood mononuclear cells (PBMC).  In MTB-stimulated PBMC SLPI levels decreased compared to non-stimulated cells, as measured by ELISA (0.175±0.13ng/ml vs 0.38± 0.15; p<0.05).  Furthermore, MTB-stimulated A549 epithelial cells decreased SLPI levels secretion compared to non-stimulated A549 cells (p<0.05). Given the importance of IFN-g production in the host response to MTB, A549 cells were treated with IFN-g and SLPI levels were analyzed.  Interestingly, IFN-g-stimulation reduced SLPI production in a dose dependent manner (control: 28.3±2.8; 0.2ng/ml 12.6±2.4; 2ng/ml 7.43±3.82*; 20ng/ml 3.79±1.99 ng/ml**; p<0.05).  Moreover, rhSLPI influenced MTB-induced IFN-g by PBMC by diminishing IFN-g production at 24hs (control: 543.08 ±113.4; SLPI: 232.9±102.56) and 48hs (control: 4761.76 ±1400; SLPI: 1629±456).  Furthermore, since SLPI- treatment reduced the proteolitic degradation of IkB induced by MTB , we speculate that the reduction of IFN-g levels by SLPI might be an effect mediated by a decrease in the translocation of NFkB to the nucleus.  Overall, our data  show that SLPI modulates IFN-g response against MTB.