Up‐regulation of inflammatory reactions by MPT32, a secreted protein of Mycobacterium tuberculosis in RAW264.7 macrophages

• Published in: Journal of cellular biochemistry 2023-09, Vol.124 (9), p.1423-1434
• Main Authors: Kim, Hee‐Do, Choi, Hyunju, Abekura, Fukushi, Park, Junyoung, Cho, Seung‐Hak, Lee, Young‐Choon, Kim, Cheorl‐Ho
• Format: Article
• Language: English
• Subjects: Antigenicity; Drug development; Environmental changes; Gene expression; Global health; Immune response; Immunogenicity; Immunomodulation; Inflammation; Lipopolysaccharides; Macrophages; MAP kinase; Metalloproteinase; Multidrug resistance; Mycobacterium tuberculosis; Nitric oxide; Nitric-oxide synthase; Prostaglandin endoperoxide synthase; Proteins; Public health; Translocation; Tuberculosis; Tumor necrosis factor-TNF; Vaccines
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.30456

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and is still one of the global health burdens. The occurrence of various cases and multidrug resistance confirm that TB has not been completely conquered. For these reasons, the present research has been conducted to explore TB vaccine and drug candidate possibility using Mtb‐secreted proteins. Among these proteins, MPT32 is known to have antigenicity and immunogenicity. There has not been a report on the host immune responses and regulation in macrophage cells. The present study was conducted with MPT32 in RAW 264.7 murine macrophage cells that control immune responses by sensing pathogen invasion and environmental change. We have found that MPT32 could activate lipopolysaccharide (LPS)‐induced gene expression of metalloproteinase‐9 (MMP‐9) and inflammation in RAW 264.7 cells. After treating cells with MPT32, the increase in pro‐inflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β (IL‐1β) and IL‐6, was observed. In addition, activated macrophages expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) to generate various inflammatory mediator molecules, such as nitric oxide (NO). The increase in iNOS and COX‐2 levels, which are up‐regulators of MMP‐9 expression, was also confirmed. The biochemical events are involved in the downstream of activated MAPK signaling and translocation of NF‐ κ B transcription factor. The present results prove the immunomodulatory effect of MPT32 in the RAW 264.7 murine macrophage cells. it claims the possibility of a TB vaccination and drug candidate using MPT32, contributing to the prevention of TB.