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Updated: Apr 28, 2026
Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
FIP200 is involved in murine pseudomonas infection by regulating HMGB1 intracellular translocation
Yi Li1, Chang-pei Gan, Shuang Zhang
1State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Background:
FIP200, a critical autophagy initiating protein, can participate in numerous cellular functions including cancer development; however, its functional role in P. aeruginosa infection of alveolar macrophages is unknown.
Methods:
To investigate the role of FIP200 in host defense, we transfected murine alveolar macrophage MH-S cells with FIP200 siRNA. Having confirmed that FIP200 knockdown inhibited PAO1-induced autophagosme formation, we sought to characterize the underlying signaling pathways by immunoblotting. Further, we used fip200 KO mice to study the effects of fip200 deficiency on HMGB1 translocation.
Results:
We showed that Pseudomonas PAO1 strain infection facilitated autophagosome formation, whereas knockdown of FIP200 inhibited autophagosome formation and HMGB1 expression in MH-S cells. Silencing FIP200 impaired the translocation of HMGB1 to cytosol of MH-S cells and almost abolished acetylation of HMGB1 during PAO1 infection. In contrast, FIP200 overexpression facilitated the cytosol translocation of HMGB1 from nuclei and increased acetylation of HMGB1 in PAO1-infected MH-S cells. Importantly, expression and acetylation of HMGB1 were also significantly down-regulated in fip200 KO mice following PAO1 infection.
Conclusions:
Collectively, these findings elucidate that FIP200 may regulate expression and translocation of HMGB1 during PAO1 infection, which may indicate novel therapeutic targets to control pulmonary infection.
Insights
FIP200 protein regulates HMGB1 expression and translocation in macrophages during Pseudomonas aeruginosa infection. This finding offers potential therapeutic targets for pulmonary infections.
Area of Science:
- Cellular Biology
- Immunology
- Microbiology
Background:
- FIP200 is a key protein in autophagy initiation and is implicated in cancer.
- The role of FIP200 in Pseudomonas aeruginosa (PAO1) infection of alveolar macrophages remains unclear.
Purpose of the Study:
- To investigate the function of FIP200 in host defense against PAO1 infection.
- To elucidate the molecular mechanisms involving FIP200, autophagy, and HMGB1 during PAO1 infection.
Main Methods:
- Utilized FIP200 siRNA in murine alveolar macrophage MH-S cells.
- Confirmed FIP200 knockdown effects on PAO1-induced autophagosome formation via immunoblotting.
- Employed fip200 knockout (KO) mice to assess HMGB1 translocation.
Main Results:
- PAO1 infection induced autophagosome formation, which was inhibited by FIP200 knockdown.
- FIP200 silencing impaired HMGB1 translocation to the cytosol and abolished its acetylation during PAO1 infection.
- FIP200 deficiency in mice significantly reduced HMGB1 expression and acetylation post-PAO1 infection.
Conclusions:
- FIP200 regulates HMGB1 expression and translocation in macrophages during PAO1 infection.
- These findings suggest FIP200 and HMGB1 as potential therapeutic targets for pulmonary infections.
