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The study on proinflammatory effect of Mycobacterium tuberculosis PE_PGRS60 protein through JNK-COX2 axis / 中华微生物学和免疫学杂志
Chinese Journal of Microbiology and Immunology ; (12): 289-294, 2021.
Article in Chinese | WPRIM | ID: wpr-885671
ABSTRACT

Objective:

To investigate the mechanism of PE_PGRS60 protein in the pathogenesis of Mycobacterium tuberculosis infection.

Methods:

The cloned and purified PE_PGRS60 protein from Mycobacterium tuberculosis was used to stimulate RAW264.7 cells. The expression of cyclooxygenase 2(COX2) mRNA and protein was detected by qRT-PCR and Western blot, respectively. The signal pathways that may regulate the expression of COX2 were screened, and the expression of inflammatory cytokines induced by PE_PGRS60 was detected by ELISA. The level of cell death was measured by lactate dehydrogenase(LDH) release test and flow cytometry PI staining. Western blot was used to detect the expression of COX2 in Peripheral blood mononuclear cell(PBMC) from active tuberculosis patients.

Results:

PE_PGRS60 protein was found to promote the expression of COX2 in RAW264.7 cells and activate the three major members of the mitogen-activated protein kinase(MAPK) family extracellular regulated protein kinase(ERK), p38 and c-Jun N-terminal kinase(JNK). Interestingly, only JNK-IN-7, the inhibitor of JNK was observed to suppress the up-regulation expression of COX2 induced by PE_PGRS60. This up-regulated expression of COX2 was also found in PBMCs from active tuberculosis patients. The COX2 inhibitor celecoxib can effectively block the expression of the inflammatory factors IL-1β, TNF-α and IL-6 induced by PE_PGRS60 and promote macrophage death.

Conclusions:

PE_PGRS60 can promote macrophages to release inflammatory factors by activating JNK/COX2 signal axis. Some macrophages still die under the protection of COX2.
Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Microbiology and Immunology Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Microbiology and Immunology Year: 2021 Type: Article