NF-κB repressing factor inhibits chemokine synthesis by peripheral blood mononuclear cells and alveolar macrophages in active pulmonary tuberculosis.
NF-κB repressing factor (NRF) is a transcriptional silencer implicated in the basal silencing of specific NF-κB targeting genes, including iNOS, IFN-β and IL-8/CXCL8. IP-10/CXCL10 and IL-8/CXCL8 are involved in neutrophil and lymphocyte recruitment against M. tuberculosis (MTb) and disease progression of pulmonary tuberculosis (TB). Alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) were used to study the regulatory role of NRF in pulmonary TB. AM and PBMC were purified from 19 TB patients and 15 normal subjects. To study the underlying mechanism, PBMC were exposed to heated TB bacilli. The regulation role of NRF in IP-10/CXCL10 and IL-8/CXCL8 was determined by NRF knock-down or over-expression. NRF binding capabilities in promoter sites were measured by chromatin immunoprecipitation (ChIP) assay. The levels of IP-10/CXCL10, IL-8/CXCL8 and NRF were significantly higher in AM and PBMC in patients with active TB. NRF played an inhibitory role in IP-10/CXCL10 and IL-8/CXCL8 inductions. We delineate the role of NRF in pulmonary TB, which inhibits the expressions of IP-10/CXCL10 and IL-8/CXCL8 in AM and PBMC of patients with high bacterial load. NRF may serve as an endogenous repressor to prevent robust increase in IP-10/CXCL10 and IL-8/CXCL8 when TB bacterial load is high.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Kuo-Hsiung
KH
Huang
Chun-Hua
CH
Wang
Kang-Yun
KY
Lee
Shu-Min
SM
Lin
Chien-Huang
CH
Lin
Han-Pin
HP
Kuo
D000328:Adult; D058491:Bacterial Load; D001483:Base Sequence; D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology
D018925:Chemokines; C111027:NKRF protein, human; D012097:Repressor Proteins