Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies

Xu, Jiangmei; Chen, Hao; Qian, Haisheng; Wang, Fei; Xu, Yunsheng

doi:10.1186/s12951-022-01651-y

Table 1 The pathogenetic role of ROS in dysfunctional different cell types (KCs, skin-resident and -infiltrating immune cells functions) mediated propagation of inflammatory loops in the EIME of psoriasis

From: Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies

Cell type	Oxidative stress state	The target of ROS/RNS modification/signaling pathways	Molecular mechanism	References
Keratinocyte	ROS↑	NADPH oxidases (NOX)↑	ROS-NOX-psoriasis signatures of cytokines-keratinocyte hyperproliferation (PS)	[16]
Keratinocyte	ROS↑	mTOR- NF-κB pathway	TNF-α induced-ROS activated mTOR-NF-κB pathway and then increases the production of inflammatory cytokines	[28]
Keratinocyte	ROS↑	ROS-NOX1/NOX4-pro-inflammatory cytokines	NOX1/NOX4 inhibitors could decrease the production of ROS to relieve the AD and PSO inflammation	[16]
Keratinocyte	ROS↑	p47-NOX-ROS-NF-κB/cyclin D1pathway	PDE4 inhibitor could improve psoriasis via inactivation of p47 subunit protein	[41]
Keratinocyte	ROS↑	ROS-SIRT1-NF-κB signaling	Chemerin/ChemR23 axis evoked the inflammatory response of psoriatic KCs through inhibiting and promoting the activation of downstream gene NF-κB by ROS production	[48]
Keratinocyte	ROS↑	ROS-NF-κB/MAPK signaling	The decreased levels of GSH, SOD and CAT, and MDA in IMQ-induced psoriatic skin tissue were detoxified by cimifugin by inactivating NF-κB/MAPK signaling pathway	[49]
Keratinocyte	ROS↑	SIRT1-MAPK/NF-κB/STAT3	Salidroside inhibited ROS-mediated MAPK/NF-κB/STAT3 singling pathway via SIRT1 activation to ameliorate psoriasis	[32]
Keratinocyte	ROS↑	SIRT1-NF-κB/MAPK	Catalpol suppressed ROS-induced inflammatory response via up-regulation of SIRT1 to block the ROS-associated NF-κB and MAPKs signaling pathways	[47]
Keratinocyte	ROS↑	TNF-α/IL-17 A-ROS- NF-κB	Astilbin/ Galangin relieved psoriasis-like skin inflammation via neutralizing harmal ROS to induce Nrf2 expression	[54, 55]
Keratinocyte	ROS↑	ROS-STAT3-HO-1	HO-1 restrained STAT3 activation through upregulation of SHP-1 expression to reverse Stat3-controlled aberrant keratinocyte differentiation	[51]
Keratinocyte	ROS↑	ROS-NRF2/HO-1	DMF attenuated oxidative distress and repaired cellular total antioxidant capability via activating the NRF2 pathway	[147]
Keratinocyte	ROS↑(H₂O₂) produced by membrane NADPH oxidase 2 (Nox2) under the stimulation of TNF-α	H₂O₂- AQP3-NF-κB	H₂O₂ transport could be facilitated by AQP3 to the promotion of the NF-κB activation in KCs for the development of psoriasis	[58]
Keratinocyte	ROS↑	ROS-mTOR signaling- proinflammatory cytokines	Rapamycin could attenuate proinflammatory cytokines in psoriatic mouse lesional skin via inhibiting oxidant signaling-related factors NOX2/4 and increasing the expression of antioxidant transcriptional factor NRF2	[40]
Keratinocyte	ROS↑	GPR43-DUOX2-ROS signaling cascades	GPR43-mediated epidermal DUOX2 and IL-6 signaling generated ROS to aggravate psoriatic inflammation	[42]
MDSCs	ROS↑	ROS-GSH-the inability of MDSCs differentiation	MDSCs from IMQ psoriatic mice model exhibited downregulation of GSH and disturbing MDSCs differentiation into CD11c⁺MHC-II⁺ dendritic cells and CD206⁺ M2 macrophages	[65]
Macrophage and ILC3	Superoxide/ NO↑(ROS/RNS)	NOS2 (nitric oxide synthase) ↑	Mannan-induced NOS2-macrophage-derived IL1α- up-regulation level of IL-17 A in a subset of skin ILC3 (innate lymphocytes) (MIP)	[67]
RAW264.7	ROS↑	ROS-NF-κB/ERK/JNK signaling pathway- inflammatory cytokines	IMQ induced upregulation of iNOS, NF-κB and MAPKs signaling cascade with a concomitant increase in the expression of inflammatory cytikines in skin tissues	[66]
LCs	ROS↑	ROS-autophagy-NF-κB and MAPK14/p38-IL-23 A	Drug-provoked inflammatory reactions through suppression of autophagy in epidermal LCs and dermal DCs to promote the secretion of IL23A under sterile-inflammatory conditions	[74]
PBMC	ROS↑	TNFα + IL-17 A-ROS-NLRP3- pro-IL-18 and pro-IL-1β	TNF-α stimulated the NLRP3 inflammasome mediated signaling pathway in PBMC from psoriasis patients via ROS and casepase1/8	[73]
PBMC(CD10^negCD16^negCD11b^neg/low neutrophils)	ROS↑	TNF-α + f-MLF-ROS-aged neutrophils- an increase of T cells-associated proinflammatory cytokines expression	Blood-derived CD10^neg immature and CD10^neg aged neutrophils promoted the proinflammatory cytokine expression by T cells in vitro through NETosis mediated by ROS	[91]
Polymorphonuclear granulocytes	ROS↑	PMA-ROS-NETs formation	DMF inhibited NET formation in a GSH-depletion and ROS-limitation manner of polymorphonuclear granulocytes	[129]
Dendritic cell	mtROS↑	IMQ-p32/C1qbp-mtROS- DC hyperactivation and inflammasome	p32/C1qbp-dependent mtROS pathway induced IL-23-mediated psoriatic inflammation through DC activation	[95]
Dendritic cell	ROS↑	ROS-induced GSH depletion-OH-1 activation and STAT1 phosphorylation damage	Small molecules of fumarates induced type II DCs in mice and in humans to ameliorate psoriasis via GSH depletion.	[76]
Memory CD4⁺ T cells	ROS↑	ROS- CAT/ SOD1/2/TAC reduction in activated memory CD4⁺ T cells	Imbalance redox status in activated memory CD4 + T cells involved in the pathogenesis of psoriasis	[99]
γδ T cells	ROS↑	ROS-8-oxo-dGTP accumulation and oxidative DNA-Th17-associated cytokines-IL-17-producing γδ T cells in lymph nodes	Oxidized nucleotides induced by ROS contributed to the activation of Th17 cells, accompanied by elevated IL-17-producing γδ T cells	[102]
Mouse CD4⁺ T cell	ROS↑	ROS- CD4⁺ T cell polarization to Th2 and Th17	Differentiation of CD4⁺ T cells into Th2 and Th17 cell subsets could be restrained by the intracellular ROS-scavenging ability of Astragalus sinicus L.	[101]
ILCs	ROS↑	Nos2-derived NO-IL-17-producing ILC3	IL-17-producing ILC3 was upregulated by Nos2-derived NO to exacerbate psoriasis-like inflammation in MIP mice molde	[67]

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