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Psoriasiform Inflammation Is Associated with Mitochondrial Fission/GDAP1L1 Signaling in Macrophages
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 19, International Journal of Molecular Sciences, Vol 22, Iss 10410, p 10410 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- While psoriasis is known as a T cell- and dendritic cell-driven skin inflammation disease, macrophages are also reported to play some roles in its development. However, the signaling pathway of activated macrophages contributing to psoriasis is not entirely understood. Thus, we aimed to explore the possible mechanisms of how macrophages initiate and sustain psoriasis. The differentiated THP1 cells, stimulated by imiquimod (IMQ), were utilized as the activated macrophage model. IMQ was also employed to produce psoriasis-like lesions in mice. A transcriptomic assay of macrophages revealed that the expressions of pro-inflammatory mediators and GDAP1L1 were largely increased after an IMQ intervention. The depletion of GDAP1L1 by short hairpin (sh)RNA could inhibit cytokine release by macrophages. GDAP1L1 modulated cytokine production by activating the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways. Besides GDAP1L1, another mitochondrial fission factor, Drp1, translocated from the cytosol to mitochondria after IMQ stimulation, followed by the mitochondrial fragmentation according to the immunofluorescence imaging. Clodronate liposomes were injected into the mice to deplete native macrophages for examining the latter’s capacity on IMQ-induced inflammation. The THP1 cells, with or without GDAP1L1 silencing, were then transplanted into the mice to monitor the deposition of macrophages. We found a significant THP1 accumulation in the skin and lymph nodes. The silencing of GDAP1L1 in IMQ-treated animals reduced the psoriasiform severity score from 8 to 2. After depleting GDAP1L1, the THP1 recruitment in the lymph nodes was decreased by 3-fold. The skin histology showed that the GDAP1L1-mediated macrophage activation induced neutrophil chemotaxis and keratinocyte hyperproliferation. Thus, mitochondrial fission can be a target for fighting against psoriatic inflammation.
- Subjects :
- Mitochondrial fission factor
THP-1 Cells
QH301-705.5
medicine.medical_treatment
T cell
Inflammation
macrophage
Drp1
Mitochondrion
Mitochondrial Dynamics
Article
Catalysis
GDAP1L1
Mitochondrial Proteins
Inorganic Chemistry
Mice
medicine
Animals
Humans
Macrophage
Physical and Theoretical Chemistry
Biology (General)
Molecular Biology
QD1-999
Spectroscopy
Mice, Inbred BALB C
Chemistry
Macrophages
mitochondrial fission
Organic Chemistry
General Medicine
psoriasis
Computer Science Applications
Cell biology
imiquimod
medicine.anatomical_structure
Cytokine
Female
Mitochondrial fission
medicine.symptom
Keratinocyte
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....66507b1de88870ee007ad7dc955a15bc
- Full Text :
- https://doi.org/10.3390/ijms221910410