Mycobacterium tuberculosis-Secreted Protein, ESAT-6, Inhibits Lipopolysaccharide-Induced MMP-9 Expression and Inflammation Through NF-κB and MAPK Signaling in RAW 264.7 Macrophage Cells

被引:16
作者
Ha, Sun-Hyung [1 ]
Choi, Hyunju [1 ]
Park, Jun-Young [1 ]
Abekura, Fukushi [1 ]
Lee, Young-Choon [2 ]
Kim, Jeong-Ran [3 ]
Kim, Cheorl-Ho [1 ]
机构
[1] Sungkyunkwan Univ, Dept Biol Sci, Mol & Cellular Glycobiol Unit, Kyunggi Do 16419, South Korea
[2] Dong A Univ, Fac Med Biotechnol, Busan, South Korea
[3] Korean Inst TB, Dept Res & Dev, 168-5 Osongsaengmyeong4 Ro, Cheongju 28158, Chungcheongbuk, South Korea
关键词
Mycobacterium tuberculosis; ESAT-6; inflammation; RAW; 264; 7 macrophage cells; DRUG-RESISTANT TUBERCULOSIS; MATRIX-METALLOPROTEINASE-9; EXPRESSION; ANTIGEN; BOVIS; IDENTIFICATION; RD1; ACTIVATION; RESPONSES; URINE; ALPHA;
D O I
10.1007/s10753-019-01087-x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
-20pt?>Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium that causes contagious tuberculosis (TB). Recently, Mtb-secreted proteins have been considered virulence factors and candidates for drugs and vaccines. Among these proteins, 6-kDa early secreted antigenic target (ESAT-6) is known to be able to induce component of matrix metalloproteinase-9 (MMP-9) in epithelial cells, leading to recruitment of macrophages. However, detailed function of ESAT-6 during macrophage recruitment to inflammatory sites remains unknown. Thus, the objective of the present study was to elucidate such function of EAST-6 and mechanism(s) involved. In the present study, we have found that recombinant ESAT-6 purified in the form of ESAT-6 double-connected structure (2E6D) could inhibit lipopolysaccharide (LPS)-induced potential of cell migration and inflammation in murine macrophage cells. Interestingly, 2E6D suppressed LPS-induced MMP-9 expression at both protein and mRNA levels as well as its enzyme activity. Levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes as known upregulators of MMP-9 were significantly decreased when 2E6D has been treated. In addition, nitric oxide (NO) as a second messenger was also significantly decreased by treatment with the purified 2E6D. Furthermore, 2E6D inhibited LPS-induced phosphorylation of I kappa B and translocation of NF-kappa B. Moreover, 2E6D suppressed phosphorylation of MAPK signaling proteins. Taken together, these results suggest that ESAT-6 can suppress LPS-induced MMP-9 and inflammation by downregulating COX-2, iNOS, and NO through NF-kappa B and MAPK signaling.
引用
收藏
页码:54 / 65
页数:12
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