Macrophage signaling in HIV-1 infection

The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection

PLACEBO-CONTROLLED STUDY OF THE EFFECTS OF 3-MONTH LYMECYCLINE TREATMENT ON SERUM MATRIX METALLOPROTEINASES IN REACTIVE ARTHRITIS

LAUHIO A, KONTTINEN YT, SALO T, et al. PLACEBO-CONTROLLED STUDY OF THE EFFECTS OF 3-MONTH LYMECYCLINE TREATMENT ON SERUM MATRIX METALLOPROTEINASES IN REACTIVE ARTHRITIS. In: INHIBITION OF MATRIX METALLOPROTEINASES: THERAPEUTIC POTENTIAL. Annals of the New York Academy of Sciences. Vol 732. NEW YORK ACAD SCIENCES; 1994: 424-426

THE IN-VIVO EFFECT OF DOXYCYCLINE TREATMENT ON MATRIX METALLOPROTEINASES IN REACTIVE ARTHRITIS

LAUHIO A, KONTTINEN YT, SALO T, et al. THE IN-VIVO EFFECT OF DOXYCYCLINE TREATMENT ON MATRIX METALLOPROTEINASES IN REACTIVE ARTHRITIS. In: INHIBITION OF MATRIX METALLOPROTEINASES: THERAPEUTIC POTENTIAL. Vol 732. NEW YORK ACAD SCIENCES; 1994: 431-432

REDUCTION OF MATRIX METALLOPROTEINASE 8-NEUTROPHIL COLLAGENASE LEVELS DURING LONG-TERM DOXYCYCLINE TREATMENT OF REACTIVE ARTHRITIS

LAUHIO A, KONTTINEN YT, Tschesche H, et al. REDUCTION OF MATRIX METALLOPROTEINASE 8-NEUTROPHIL COLLAGENASE LEVELS DURING LONG-TERM DOXYCYCLINE TREATMENT OF REACTIVE ARTHRITIS. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 1994;38(2):400-402.The aim of this work was to determine whether human polymorphonuclear neutrophilic interstitial collagenase (matrix metalloproteinase 8 [MMP-8]) levels are reduced during long-term doxycycline treatment in humans with reactive arthritis. Serum MMP-8 levels were reduced (mean +/- standard error of the mean, 678.9 +/- 185.6 versus 491.2 +/- 144.8 ng of MMP-8 per ml), but not statistically significantly. However, the reduction of salivary MMP-8 levels was statistically significant (3,729 +/- 1,905.3 versus 1,866 +/- 780.0 ng of MMP-8 per ml, P < 0.05). This study demonstrated that a 2-month regimen of doxycycline can reduce MMP-8 levels in serum and especially in body fluids (i.e., saliva) containing inflammatory exudates and thus may contribute to reduced tissue destruction

Isolation of Mycobacterium avium complex from water in the United States, Finland, Zaire, and Kenya.

Disseminated infection with organisms of the Mycobacterium avium complex (MAC) is a common complication of AIDS in the United States and other developing countries, but it is rare or absent in sub-Saharan Africa. To assess the comparative likelihood of exposure to MAC in these geographic areas, we used a standard protocol to culture 91 water samples from environmental sites and piped water supply systems in the United States, Finland, Zaire, and Kenya. MAC was isolated from all geographic areas and from 22 of 91 (24%) samples. Isolation rates were 13 of 47 (28%) for environmental samples and 9 of 44 (20%) for water supply samples. Overall isolation rates were 18 of 52 (35%) samples in the United States and Finland, whereas they were 4 of 39 (10%) samples in Zaire and Kenya (P = 0.015). MAC isolation rates from water supply systems were 8 of 25 (32%) samples in the United States and Finland and 1 of 19 (5%) samples in Zaire and Kenya (P = 0.056). MAC was isolated from hospital water in the United States and Finland but not in hospital water in Zaire and Kenya. Serovar determinations showed that six of eight isolates from the United States were serovar 4 or 8. One MAC isolate from Zaire was identified as an "X" mycobacterium. These data suggest that exposure to MAC in water is likely in diverse areas of the world, but that the likelihood of human exposure to the organism in water may be slightly less in sub-Saharan Africa than in developed countries in the Northern Hemisphere