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Article

Psoriasiform Inflammation Is Associated with Mitochondrial Fission/GDAP1L1 Signaling in Macrophages

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Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
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Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan
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Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan
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Tissue Bank, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan
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Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
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Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan 333, Taiwan
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Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editors: Bogusław Nedoszytko, Agnieszka Owczarczyk-Saczonek, Dorota Krasowska and Aneta Szczerkowska-Dobosz
Int. J. Mol. Sci. 2021, 22(19), 10410; https://doi.org/10.3390/ijms221910410
Received: 10 September 2021 / Revised: 22 September 2021 / Accepted: 23 September 2021 / Published: 27 September 2021
(This article belongs to the Special Issue New Insights into Psoriasis)
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. View Full-Text
Keywords: psoriasis; macrophage; mitochondrial fission; GDAP1L1; Drp1; imiquimod psoriasis; macrophage; mitochondrial fission; GDAP1L1; Drp1; imiquimod
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MDPI and ACS Style

Alalaiwe, A.; Chen, C.-Y.; Chang, Z.-Y.; Sung, J.-T.; Chuang, S.-Y.; Fang, J.-Y. Psoriasiform Inflammation Is Associated with Mitochondrial Fission/GDAP1L1 Signaling in Macrophages. Int. J. Mol. Sci. 2021, 22, 10410. https://doi.org/10.3390/ijms221910410

AMA Style

Alalaiwe A, Chen C-Y, Chang Z-Y, Sung J-T, Chuang S-Y, Fang J-Y. Psoriasiform Inflammation Is Associated with Mitochondrial Fission/GDAP1L1 Signaling in Macrophages. International Journal of Molecular Sciences. 2021; 22(19):10410. https://doi.org/10.3390/ijms221910410

Chicago/Turabian Style

Alalaiwe, Ahmed, Chi-Yuan Chen, Zi-Yu Chang, Jui-Tai Sung, Shih-Yi Chuang, and Jia-You Fang. 2021. "Psoriasiform Inflammation Is Associated with Mitochondrial Fission/GDAP1L1 Signaling in Macrophages" International Journal of Molecular Sciences 22, no. 19: 10410. https://doi.org/10.3390/ijms221910410

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