DUSP1 mediates BCG induced apoptosis and inflammatory response in THP-1 cells via MAPKs/NF-κB signaling pathway

Abstract

Tuberculosis (TB) is a zoonotic infectious disease caused by Mycobacterium tuberculosis (Mtb). Apoptosis and necrosis caused by the interaction between the host and the pathogen, as well as the host’s inflammatory response, play an important role in the pathogenesis of TB. Dual-specificity phosphatase 1 (DUSP1) plays a vital role in regulating the host immune responses. However, the role of DUSP1 in the regulation of THP-1 macrophage apoptosis induced by attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection remains unclear. In the present study, we report that infection with BCG significantly induces macrophage apoptosis and induces the production of DUSP1, TNF-α and IL-1β. DUSP1 knockdown significantly inhibited BCG-induced macrophage apoptosis and activation of MAPKs/NF-κB signaling pathway. In addition, DUSP1 knockdown suppressed BCG-induced inflammation in vivo. Taken together, this study demonstrates that DUSP1, as a regulator of MAPKs/NF-κB signaling pathway, plays a novel role in BCG-induced macrophage apoptosis and inflammatory response.

Identification and Validation of Genes Related to Macrophage Polarization and Cell Death Modes Under Mycobacterium tuberculosis Infection

“… 30 In addition, the inflammatory factor TNF activates the NF-kappaB signaling pathway centered on NFKB1 to induce apoptosis and inflammatory responses in Mφ. 31 , 32 In addition, NFKB1 activates autophagy by upregulating the transcription of Beclin 1 (a key autophagy gene). 33 Whereas the onset of ferroptosis is induced by activation of IL-6/ferritin signaling, 34 and negatively regulated by RELA.…”

Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota–gut–brain axis in corticosterone combined with chronic restraint stress‐induced mice

“…51 Dusp1 could promote downstream ERK/BDNF signaling to treat depression 52 and MAPKs/NF-κB signaling to decrease the level of TNF-α. 53 Overexpression of Dusp1 is vital to the physiology of stress and linked to a depressive-like phenotype, which is a common feature of various rodent chronicstress-based models of depression. 54 In the intestinal flora analysis for the ZZCD anti-depression and anxiety effect we found a significant increase in alpha index in the Model group, ZZCD group and Ven group suggesting successful establishment of animal models.…”

“…Dusp1 overexpression appears to be connected to chronic stress 51 . Dusp1 could promote downstream ERK/BDNF signaling to treat depression 52 and MAPKs/NF‐κB signaling to decrease the level of TNF‐α 53 . Overexpression of Dusp1 is vital to the physiology of stress and linked to a depressive‐like phenotype, which is a common feature of various rodent chronic‐stress‐based models of depression 54…”

Host‐pathogen dialogues in different cell death modes during Mycobacterium tuberculosis infection

“…In addition to classical apoptotic proteins, dualspecificity phosphatases are members of the protein tyrosine phosphatase superfamily, which can participate in BCG-induced THP-1 MAPKs/NF-κ B signaling and mediate apoptosis. 30 Another important approach for pathogens and hosts to remodel transcriptomes is alternative splicing. Recent studies have shown that UBE2B, a ubiquitin-conjugating enzyme, and host UBE2B-exon7skipping exon (SE) predict tuberculosis and are closely associated with apoptosis onset.…”