PMID- 27154637
OWN - NLM
STAT- MEDLINE
DCOM- 20170130
LR  - 20170130
IS  - 1365-3083 (Electronic)
IS  - 0300-9475 (Linking)
VI  - 84
IP  - 1
DP  - 2016 Jul
TI  - Early Secreted Antigenic Target of 6 kDa of Mycobacterium tuberculosis Stimulates 
      Macrophage Chemoattractant Protein-1 Production by Macrophages and Its Regulation 
      by p38 Mitogen-Activated Protein Kinases and Interleukin-4.
PG  - 39-48
LID - 10.1111/sji.12447 [doi]
AB  - Early secreted antigenic target of 6 kDa (ESAT-6), the major virulence factor of 
      Mycobacterium tuberculosis, affects host immunity and the formation of granulomas 
      likely through inflammatory cytokines. To understand its role in this regard 
      further, we investigated the effect of ESAT-6 on macrophages by determining the 
      production of macrophage chemoattractant protein (MCP)-1, a major chemokine 
      associated with tuberculosis pathogenesis, by murine bone marrow-derived 
      macrophages (BMDMs) and its regulation by protein kinases and cytokines. The 
      results revealed that ESAT-6, but not Ag85A and culture filtrate protein 10 kDa 
      (CFP10), induced MCP-1 production by BMDMs dose and time dependently. Inhibition 
      of p38 but not other mitogen-activated protein kinases (MAPK) and PI3K further 
      enhanced ESAT-6-induced MCP-1 production by BMDMs. Inhibition of p38 MAPK 
      enhanced ESAT-6-induced MCP-1 mRNA accumulation without affecting mRNA stability. 
      ESAT-6 also induced TNF-alpha from BMDMs and MCP-1 from mouse lung epithelial cells, 
      and these were suppressed by p38 MAPK inhibition, implying cytokine- and 
      cell-specific effect of p38 MAPK inhibition on ESAT-6-induced MCP-1 by 
      macrophages. Pretreatment of BMDMs with IL-4, but not other cytokines (IL-2, 
      IL-10, TNF-alpha, IFN-gamma and IL-1alpha) further elevated ESAT-6-stimulated MCP-1 
      production although IL-4 did not induce MCP-1 without ESAT-6. Both p38 MAPK 
      inhibitor and IL-4 did not show additive effect on ESAT-6-induced MCP-1 protein 
      level despite such effect on MCP-1 mRNA level was evident. In conclusion, these 
      results indicate a specific role for both p38 MAPK and IL-4 in ESAT-6-induced 
      MCP-1 production by macrophages and suggest a pathway with significance in 
      tuberculosis pathogenesis.
CI  - (c) 2016 The Foundation for the Scandinavian Journal of Immunology.
FAU - Ma, J
AU  - Ma J
AD  - Department of Pulmonary Immunology, University of Texas Health Science Center at 
      Tyler, Tyler, TX, USA.
FAU - Jung, B-G
AU  - Jung BG
AD  - Department of Pulmonary Immunology, University of Texas Health Science Center at 
      Tyler, Tyler, TX, USA.
FAU - Yi, N
AU  - Yi N
AD  - Department of Pulmonary Immunology, University of Texas Health Science Center at 
      Tyler, Tyler, TX, USA.
FAU - Samten, B
AU  - Samten B
AD  - Department of Pulmonary Immunology, University of Texas Health Science Center at 
      Tyler, Tyler, TX, USA.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (ESAT-6 protein, Mycobacterium tuberculosis)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/*metabolism
MH  - Bacterial Proteins/*metabolism
MH  - Cell Line
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-4/*metabolism
MH  - Macrophages/*metabolism/microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mycobacterium tuberculosis/*immunology/pathogenicity
MH  - Respiratory Mucosa/*metabolism/pathology
MH  - Tuberculosis/*immunology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2016/05/08 06:00
MHDA- 2017/01/31 06:00
CRDT- 2016/05/08 06:00
PHST- 2016/03/06 00:00 [received]
PHST- 2016/05/04 00:00 [accepted]
PHST- 2016/05/08 06:00 [entrez]
PHST- 2016/05/08 06:00 [pubmed]
PHST- 2017/01/31 06:00 [medline]
AID - 10.1111/sji.12447 [doi]
PST - ppublish
SO  - Scand J Immunol. 2016 Jul;84(1):39-48. doi: 10.1111/sji.12447.