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

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.

The Antibiofilm Nanosystems for Improved Infection Inhibition of Microbes in Skin.

Biofilm formation is an important virulence factor for the opportunistic microorganisms that elicit skin infections. The recalcitrant feature of biofilms and their antibiotic tolerance impose a great challenge on the use of conventional therapies. Most antibacterial agents have difficulty penetrating the matrix produced by a biofilm. One novel approach to address these concerns is to prevent or inhibit the formation of biofilms using nanoparticles. The advantages of using nanosystems for antibiofilm applications include high drug loading efficiency, sustained or prolonged drug release, increased drug stability, improved bioavailability, close contact with bacteria, and enhanced accumulation or targeting to biomasses. Topically applied nanoparticles can act as a strategy for enhancing antibiotic delivery into the skin. Various types of nanoparticles, including metal oxide nanoparticles, polymeric nanoparticles, liposomes, and lipid-based nanoparticles, have been employed for topical delivery to treat biofilm infections on the skin. Moreover, nanoparticles can be designed to combine with external stimuli to produce magnetic, photothermal, or photodynamic effects to ablate the biofilm matrix. This study focuses on advanced antibiofilm approaches based on nanomedicine for treating skin infections. We provide in-depth descriptions on how the nanoparticles could effectively eliminate biofilms and any pathogens inside them. We then describe cases of using nanoparticles for antibiofilm treatment of the skin. Most of the studies included in this review were supported by in vivo animal infection models. This article offers an overview of the benefits of nanosystems for treating biofilms grown on the skin.