Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial vaginosis (BV), a common condition in women, is associated with increased shedding of HIV in the female genital tract. While the Lactobacillus species that comprise a healthy vaginal microbiota produce lactic acid, the bacteria common in BV produce high concentrations of short chain fatty acids (SCFAs) and succinic acid. Macrophages are abundant in the lower genital tract mucosa and are thought to play an important role in HIV infection. In this study, we investigated whether SCFAs and succinic acid impacted HIV expression in monocyte-derived macrophages. Monocytes differentiated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF) were infected with either HIVBal or an HIV-luciferase reporter virus and treated with SCFAs, succinic acid, or lactic acid. Butyric acid suppressed HIV expression while succinic acid significantly increased expression in macrophages differentiated with either GM-CSF or M-CSF. Acetic, propionic, and lactic acids had no effect on HIV expression. Only succinic acid resulted in a significant increase in interleukin-8 production by infected macrophages. Our results suggest that succinic acid present in increased concentrations in the genital tract of women with BV plays a pro-inflammatory role and increases HIV expression. This could be one factor contributing to increased virus shedding seen in women with BV.
...
PMID:Effects of Succinic Acid and Other Microbial Fermentation Products on HIV Expression in Macrophages. 2408 94

Studies have implicated Gardnerella vaginalis as an important etiological agent in bacterial vaginosis (BV). It produces a cholesterol-dependent cytolysin, vaginolysin (VLY). In this study, we sought to characterize the interaction between vaginal epithelium, G. vaginalis, and VLY using EpiVaginal tissues from MatTek. These tissues are three-dimensional and have distinct apical and basolateral sides, enabling comparison of the effects of G. vaginalis and VLY following exposure to either side. We measured cytotoxicity, cytokine production, and bacterial growth, following apical versus basolateral exposure. G. vaginalis exhibited more-rapid growth in coculture with the tissue model when it was exposed to the apical side. VLY permeabilized cells on the basolateral side of the tissues but failed to permeabilize apical epithelial cells. Cytokine secretion in response to VLY and G. vaginalis also depended on the polarity of exposure. VLY did not cause significant changes in cytokine levels when exposed apically. Apical tissue challenge by G. vaginalis appeared to dampen the inflammatory response, as decreases in granulocyte-macrophage colony-stimulating factor (GM-CSF) (6.6-fold), RANTES (14.8-fold), and interferon gamma inducible protein 10 kDa (IP-10) (53-fold) and an increase in interleukin-1 receptor antagonist (IL-1ra) (5-fold) were observed. In vivo, G. vaginalis normally colonizes the apical face of the vaginal epithelium. Results from this study suggest that while G. vaginalis may grow on the apical face of the vaginal epithelium, its VLY toxin does not target these cells in this model. This phenomenon could have important implications regarding colonization of the vagina by G. vaginalis and may suggest an explanation for the lack of an overt immune response to this organism.
 ...
PMID:Interaction of Gardnerella vaginalis and Vaginolysin with the Apical versus Basolateral Face of a Three-Dimensional Model of Vaginal Epithelium. 3069 80