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Published on: January 7, 2019
Gene expression of TRPMLs and its regulation by pathogen stimulation
Zhiqiang Xia1, Lixia Xie1, Dongyuan Li1
1School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian 463000, China.
Abstract:
The transient receptor potential mucolipin (TRPML) subfamily in mammalian has three members, namely TRPML1, TRPML2, and TRPML3, who play key roles in regulating intracellular Ca2+ homeostasis, endosomal pH, membrane trafficking and autophagy. Previous studies had shown that three TRPMLs are closely related to the occurrence of pathogen invasion and immune regulation in some immune tissues or cells, but the relationship between TRPMLs expression and pathogen invasion in lung tissue or cell remains elusive. Here, we investigated the expression distribution of three TRPML channels in mouse different tissues by qRT-PCR, and then found that all three TRPMLs were highly expressed in the mouse lung tissue, as well as mouse spleen and kidney tissues. The expression of TRPML1 or TRPML3 in all three mouse tissues had a significant down-regulation after the treatment of Salmonella or LPS, but TRPML2 expression showed a remarkable increase. Consistently, TRPML1 or TRPML3 but not TRPML2 in A549 cells also displayed a decreased expression induced by LPS stimulation, which shared a similar regulation pattern in the mouse lung tissue. Furthermore, the treatment of the TRPML1 or TRPML3 specific activator induced a dose-dependent up-regulation of inflammatory factors IL-1β, IL-6 and TNFα, suggesting that TRPML1 and TRPML3 are likely to play an important role in immune and inflammatory regulation. Together, our study identified the gene expression of TRPMLs induced by pathogen stimulation in vivo and in vitro, which may provide novel targets for innate immunity or pathogen regulation.
Insights
Transient Receptor Potential Mucolipin (TRPML) channels are highly expressed in mouse lungs. Their expression changes with pathogen invasion, suggesting TRPMLs
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The Transient Receptor Potential Mucolipin (TRPML) subfamily comprises TRPML1, TRPML2, and TRPML3, crucial for Ca2+ homeostasis, endosomal pH, membrane trafficking, and autophagy.
- Previous research links TRPMLs to pathogen invasion and immune regulation in various tissues, but their role in lung immunity remains unclear.
Purpose of the Study:
- To investigate the expression patterns of TRPML1, TRPML2, and TRPML3 in mouse tissues, particularly the lung, in response to pathogen stimulation.
- To elucidate the role of TRPML channels in innate immunity and inflammatory responses within lung cells.
Main Methods:
- Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) to assess TRPML gene expression in mouse tissues and A549 cells.
- Stimulation of cells and tissues with Salmonella and Lipopolysaccharide (LPS) to mimic pathogen invasion.
- Treatment with specific TRPML1 or TRPML3 activators to evaluate downstream inflammatory responses.
Main Results:
- All three TRPML channels were highly expressed in mouse lung, spleen, and kidney tissues.
- Salmonella or LPS treatment significantly downregulated TRPML1 and TRPML3 expression but upregulated TRPML2 in mouse tissues and A549 cells.
- Activation of TRPML1 or TRPML3 dose-dependently increased inflammatory factors IL-1β, IL-6, and TNFα.
Conclusions:
- TRPML channel expression is dynamically regulated by pathogen stimulation in lung tissues and cells.
- TRPML1 and TRPML3 appear to play significant roles in immune and inflammatory regulation within the lung.
- TRPML channels represent potential novel targets for modulating innate immunity and controlling pathogen invasion.
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