Hiroe Shiratsuch1, Marc D Basson. 1. Department of Surgery, Wayne State University, Research Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI 48201, USA. hiroesh@msn.com
Abstract
BACKGROUND: Mycobacterium avium causes disseminated infection in immunocompromised patients and triggers a process resembling Crohn's disease in goats. Colony morphotypes predict pathogenicity. Smooth-transparent (SmT) morphotypes are more virulent and induce less interleukin (IL)-1beta and IL-18 production than avirulent smooth-domed (SmD) morphotypes. Caspases are essential for IL-1beta and IL-18 production. METHODS: Caspase activation was examined in human monocytes after M. avium infection. RESULTS: Fresh monocytes constitutively expressed caspase-1 mRNA and pro-caspase-1. The M. avium infection increased monocyte caspase-1 mRNA expression. Furthermore, SmD-infected monocytes expressed 2.3-fold higher levels (P <0.05, n = 3) of activated caspases than SmT-infected monocytes. Caspase-1 inhibition significantly reduced IL-1beta production by SmT- and SmD-infected monocytes (P <0.05, n = 4). Caspase-3 inhibition inhibited IL-1beta production 43.5% +/- 8.0% (P <0.02, n = 4) by SmD-infected but not SmT-infected monocytes. CONCLUSIONS: Decreased mature IL-1beta release by SmT-infected monocytes may reflect selective induction of caspase-1 activity but not caspase-3. Differential caspase expression in monocytes after infection may contribute to M. avium pathogenicity in humans.
BACKGROUND:Mycobacterium avium causes disseminated infection in immunocompromised patients and triggers a process resembling Crohn's disease in goats. Colony morphotypes predict pathogenicity. Smooth-transparent (SmT) morphotypes are more virulent and induce less interleukin (IL)-1beta and IL-18 production than avirulent smooth-domed (SmD) morphotypes. Caspases are essential for IL-1beta and IL-18 production. METHODS: Caspase activation was examined in human monocytes after M. aviuminfection. RESULTS: Fresh monocytes constitutively expressed caspase-1 mRNA and pro-caspase-1. The M. aviuminfection increased monocyte caspase-1 mRNA expression. Furthermore, SmD-infected monocytes expressed 2.3-fold higher levels (P <0.05, n = 3) of activated caspases than SmT-infected monocytes. Caspase-1 inhibition significantly reduced IL-1beta production by SmT- and SmD-infected monocytes (P <0.05, n = 4). Caspase-3 inhibition inhibited IL-1beta production 43.5% +/- 8.0% (P <0.02, n = 4) by SmD-infected but not SmT-infected monocytes. CONCLUSIONS: Decreased mature IL-1beta release by SmT-infected monocytes may reflect selective induction of caspase-1 activity but not caspase-3. Differential caspase expression in monocytes after infection may contribute to M. avium pathogenicity in humans.
Authors: Sharmistha Banerjee; Ashok Nandyala; Raviprasad Podili; V M Katoch; K J R Murthy; Seyed E Hasnain Journal: Proc Natl Acad Sci U S A Date: 2004-08-16 Impact factor: 11.205