Affiliation:
1. Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires/CONICET , Buenos Aires , Argentina
2. División Infectología, Hospital de Clínicas “José de San Martín”, Facultad de Medicina, Universidad de Buenos Aires , Buenos Aires , Argentina
Abstract
Abstract
Background
Monocyte activation is a driver of inflammation in the course of chronic HIV infection. Prostaglandin E2 (PGE2) is known to mediate anti-inflammatory effects, notably the inhibition of tumor necrosis factor-α (TNF-α) production by monocytes. We aim to investigate the effects of PGE2 on activation of monocytes in chronic HIV infection and the mechanisms through which PGE2 modulates their inflammatory signature.
Methods
We recruited a group of people with HIV (PWH) and matched healthy uninfected persons. We compared plasma levels of PGE2, monocyte activation, and sensitivity of monocytes to the inhibitory actions mediated by PGE2.
Results
We found increased plasma levels of PGE2 in PWH, and an activated phenotype in circulating monocytes, compared with uninfected individuals. Monocytes from PWH showed a significant resistance to the inhibitory actions mediated by PGE2; the concentration of PGE2 able to inhibit 50% of the production of TNF-α by lipopolysaccharide-stimulated monocytes was 10 times higher in PWH compared with uninfected controls. Furthermore, the expression of phosphodiesterase 4B, a negative regulator of PGE2 activity, was significantly increased in monocytes from PWH.
Conclusions
Resistance to the inhibitory actions mediated by PGE2 could account, at least in part, for the inflammatory profile of circulating monocytes in PWH.
Funder
University of Buenos Aires
National Ministry of Science, Technology, and Innovation of Argentina
Fundación Florencio Fiorini
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Immunology and Allergy