P38 MAPK-dependent and YY1-mediated chemokine receptors CCR5 and CXCR4 up-regulation in U937 cell line infected by Mycobacterium tuberculosis or Actinobacillus actinomycetemcomitans

Abstract

We have found previously that the chemokine receptors CCR5 and CXCR4, which are the coreceptors of HIV, are up-regulated in human macrophage cell line U937 infected by Mycobacterium tuberculosis (MTB). This suggests another possibility to explain the co-infection of MTB and HIV. In order to detect the up-regulation of CCR5 and CXCR4 as a unique phenomenon of MTB infection or a ubiquitous phenomenon of pathogenic bacteria, we investigated the expression changes of these two chemokine receptors in macrophages attacked by another bacterium Actinobacillus actinomycetemcomitans (AA) (from mRNA level and protein level). To reveal the molecular mechanism of these expression changes, p38 MAPK special inhibitor SB203580 was used and the expression of CCR5 and CXCR4 negative regulator YY1 transfactor was analyzed. Finally, we conclude that the up-regulation of CCR5 and CXCR4 can at least partially contribute to the down-regulation of transfactor YY1 which is p38 MAPK pathway-dependent and this up-regulation has little relationship with MTB and HIV co-infection.