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Scandinavian Journal of Immunology Sep 2009HIV-infected individuals have an increased risk of invasive bacterial infections, even at early clinical stages with relatively normal CD4(+) T-cell counts. The...
HIV-infected individuals have an increased risk of invasive bacterial infections, even at early clinical stages with relatively normal CD4(+) T-cell counts. The pathogenic mechanisms behind this are not fully understood. However, an increasing number of studies indicate that HIV may impair the innate immunity to bacteria by infecting key cells of the monocyte/macrophage lineage. In this study, the effects of HIV infection on the protein profile of undifferentiated monocyte-like THP-1 cells were examined by a mass spectrometric approach based on stable isotope labelling with amino acid in cell culture (SILAC). We identified 651 proteins, of which nine proteins were down-regulated and 17 proteins were up-regulated in HIV-infected THP-1 cells as compared to uninfected controls. Most remarkably, the IL-1 receptor associated kinase 4 (IRAK-4), which is essential for virtually all TLR signalling, was suppressed, whereas the precursor for the antibiotic peptide Dermcidin was up-regulated in HIV-infected cells. Upon stimulation of either TLR2 or TLR4, the HIV-infected THP-1 cells displayed reduced TNF-alpha secretion. The HIV-induced down-regulation of IRAK-4 was reconfirmed in monocyte-derived macrophage cell cultures. These data suggests that HIV may impair the TLR signalling cascade for pathogen recognition in cells of the monocyte/macrophage lineage and thus, may reduce the ability of the innate immune system to sense invading pathogens and initiate appropriate responses.
Topics: Cell Line; Down-Regulation; HIV; HIV Infections; Humans; Immunity, Innate; Interleukin-1 Receptor-Associated Kinases; Macrophages; Monocytes; Peptides; Proteomics; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Up-Regulation
PubMed: 19703016
DOI: 10.1111/j.1365-3083.2009.02299.x -
The Journal of Investigative Dermatology Jan 1976Monocytopoiesis and blood monocytes were examined in 8 patients with disseminated chronic eczematous diseases, 8 patients with disseminated psoriasis vulgaris, and 8...
Monocytopoiesis and blood monocytes were examined in 8 patients with disseminated chronic eczematous diseases, 8 patients with disseminated psoriasis vulgaris, and 8 patients with mycosis fungoides in plaque or tumor stage. Monocytopoiesis was moderately stimulated in all these patients. The stimulation manifested itself by: (1) a rise in relative number of promonocytes in bone marrow in all patients with eczema, in 1 out of 8 patients with psoriasis, and in 7 out of 9 examinations in patients with mycosis fungoides; (2) a rise in [3H]thymidine labeling indices of medullar promonocytes (8/8 eczema, 7/7 psoriasis, 8/9 mycosis fungoides); and (3) a rise in the naphthol-AS-D-chloroacetate esterase activity of blood monocytes, indicating premature monocyte marrow egress (3/5 eczema, 7/8 psoriasis, 9/9 mycosis fungoides). In eczema and psoriasis the mean enhancement of monocytopoietic activity was similar but less pronounced than in mycosis fungoides. In the latter disease there was no correlation between measured parameters and visible skin lesions. The results were interpreted as indicative of increased monocyte consumption by pathologic, immunologic, and/or inflammatory processes.
Topics: Adult; Aged; Cell Nucleus; Eczema; Erythropoiesis; Female; Humans; Leukocyte Count; Male; Middle Aged; Monocytes; Mycosis Fungoides; Naphthol AS D Esterase; Psoriasis; Skin Neoplasms
PubMed: 1245754
DOI: 10.1111/1523-1747.ep12478028 -
Biological & Pharmaceutical Bulletin Apr 2003We examined the in vitro effects of the benzophenone derivatives garcinol, isogarcinol, and xanthochymol on cell growth in four human leukemia cell lines. All of the...
We examined the in vitro effects of the benzophenone derivatives garcinol, isogarcinol, and xanthochymol on cell growth in four human leukemia cell lines. All of the compounds exhibited significant growth suppression due to apoptosis mediated by the activation of caspase-3. A loss of mitochondrial membrane potential was found in garcinol- and isogarcinol-induced apoptosis, but not in xanthochymol-induced apoptosis. The growth inhibitory effects of isogarcinol and xanthochymol were more potent than that of garcinol, which is a well- known cytotoxic benzophenone derivative.
Topics: Apoptosis; Benzophenones; Cell Count; Cell Line, Tumor; Cytotoxins; Garcinia; HL-60 Cells; Humans; K562 Cells; Leukemia; U937 Cells
PubMed: 12673047
DOI: 10.1248/bpb.26.569